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Identification
NameCyclosporine
Accession NumberDB00091  (BIOD00003, BTD00003)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Cyclosporine is produced as a metabolite by the fungus species Cordyceps militaris. (From Martindale, The Extra Pharmacopoeia, 30th ed).

Structure
Thumb
Synonyms
SynonymLanguageCode
CiclosporinNot AvailableINN
CsANot AvailableNot Available
CyANot AvailableNot Available
Cyclosporin ANot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
GengrafAbbott Labs
Neoral Novartis
Restasis Allergan Inc.
Sandimmune Novartis
SangcyaNot Available
Brand mixturesNot Available
Categories
CAS number59865-13-3
WeightAverage: 1202.6112
Monoisotopic: 1201.841368071
Chemical FormulaC62H111N11O12
InChI KeyPMATZTZNYRCHOR-IMVLJIQENA-N
InChI
InChI=1/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+
IUPAC Name
30-ethyl-33-[(4E)-1-hydroxy-2-methylhex-4-en-1-yl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-bis(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecone
SMILES
CCC1NC(=O)C(C(O)C(C)C\C=C\C)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentCyclosporins
Alternative parentsMacrolactams; Tertiary Carboxylic Acid Amides; Secondary Alcohols; Secondary Carboxylic Acid Amides; Tertiary Amines; Polyamines; Carboxylic Acids
Substituentsmacrolactam; tertiary carboxylic acid amide; tertiary amine; secondary alcohol; carboxamide group; secondary carboxylic acid amide; carboxylic acid; polyamine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the cyclosporins. These are cyclic depsipeptides containing the cyclosporin backbone.
Pharmacology
IndicationFor treatment of transplant (kidney, liver, and heart) rejection, rheumatoid arthritis, severe psoriasis.
PharmacodynamicsUsed in immunosuppression for prophylactic treatment of organ transplants, cyclosporine exerts specific and reversible inhibition of immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T1-helper cell is the main target, although the T1-suppressor cell may also be suppressed. Sandimmune (cyclosporine) also inhibits lymphokine production and release including interleukin-2.
Mechanism of actionCyclosporine binds to cyclophilin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Cyclosporine also inhibits lymphokine production and interleukin release. In ophthalmic applications, the precise mechanism of action is not known. Cyclosporine emulsion is thought to act as a partial immunomodulator in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.
AbsorptionThe absorption of cyclosporine from the gastrointestinal tract is incomplete and variable. The extent of absorption is dependent on the individual patient, the patient population, and the formulation. The absolute bioavailability of cyclosproine administered as Sandimmune® is dependent on the patient population, estimated to be less than 10% in liver transplant patients and as great as 89% in some renal transplant patients. Compared to an intravenous infusion, the absolute bioavailability of the oral solution is approximately 30% based upon the results in 2 patients. The cyclosporine capsules and oral solution are bioequivalent. The time of peak blood concentrations (Tmax) following oral administration of cyclosporine [modified] ranged from 1.5 - 2.0 hours.
Volume of distribution

The steady state volume of distribution during intravenous dosing has been reported as 3 to 5 L/kg in solid organ transplant recipients. Cyclosporine is excreted in human milk.

Protein bindingIn the plasma, approximately 90% is bound to proteins, primarily lipoproteins. In blood, the distribution is concentration dependent. Approximately 33% to 47% is in plasma, 4% to 9% in lymphocytes, 5% to 12% in granulocytes, and 41% to 58% in erythrocytes.
Metabolism

Hepatic, extensively metabolized by the cytochrome P450 3A enzyme system in the liver. It is also metabolized in the gastrointestinal tract and kidney to a lesser degree. The metabolites are significantly less potent than the parent compound. The major metabolites (M1, M9, and M4N) result from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively.

SubstrateEnzymesProduct
Cyclosporine
Metabolite AM1Details
Route of eliminationElimination is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in the urine. Only 0.1% of the dose is excreted in the urine as unchanged drug.
Half lifeBiphasic and variable, approximately 7 hours (range 7 to 19 hours) in children and approximately 19 hours (range 10 to 27 hours) in adults.
Clearance

Following intravenous administration, the blood clearance of cyclosporine (assay: HPLC) is approximately 5 to 7 mL/min/kg in adult recipients of renal or liver allografts. Blood cyclosporine clearance appears to be slightly slower in cardiac transplant patients. The following are clearance parameters (CL/F) for select patient populations:

  • 593 ± 204 mL/min [De novo renal transplant patients, 597±174 mg/day]
  • 492 ± 140 mL/min [Stable renal transplant patients, 344±122 mg/day]
  • 577 ± 309 mL/min [De novo liver transplant, 458±190 mg/day]
  • 613 ± 196 mL/min [De novo rheumatoid arthritis, 182±55.6 mg/day]
  • 723 ± 186 mL/min [De novo psoriasis, 189±69.8 mg/day]
  • 285 ± 94 mL/min [Stable Liver Transplant, Age 2 – 8, Dosed T.I.D 101±25 mg/day]
  • 378 ± 80 mL/min [Stable Liver Transplant, Age 8 – 15, Dosed B.I.D 188±55 mg/day]
  • 171 mL/min [Stable liver transplant, Age 3, Dosed B.I.D 120 mg/day]
  • 328 ± 121 mL/min [Stable liver transplant, Age 8 – 15, Dosed B.I.D 158±55 mg/day]
  • 418 ± 143 mL/min [Stable renal transplant, Age 7 – 15, Dosed B.I.D 328±83 mg/day]
ToxicityThe oral LD50 is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD50 is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Cytotoxic T-lymphocyte protein 4
Gene symbol: CTLA4
UniProt: P16410
rs231775 Not AvailableA AlleleGingival overgrowth, periodontal disease18021981
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8727
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.6994
P-glycoprotein substrate Substrate 0.8463
P-glycoprotein inhibitor I Inhibitor 0.8685
P-glycoprotein inhibitor II Non-inhibitor 0.5992
Renal organic cation transporter Non-inhibitor 0.9485
CYP450 2C9 substrate Non-substrate 0.8628
CYP450 2D6 substrate Non-substrate 0.8823
CYP450 3A4 substrate Substrate 0.6407
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.923
CYP450 2D6 substrate Non-inhibitor 0.9265
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.6112
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9968
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.8948
Biodegradation Not ready biodegradable 0.9244
Rat acute toxicity 2.8788 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9815
hERG inhibition (predictor II) Non-inhibitor 0.9214
Pharmacoeconomics
Manufacturers
  • Apotex inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Pliva inc
  • Sandoz inc
  • Abbott laboratories
  • Novartis pharmaceuticals corp
  • Allergan inc
  • Bedford laboratories div ben venue laboratories inc
  • Pharmaforce inc
  • Novex pharma
  • Watson laboratories inc
  • Wockhardt eu operations (swiss) ag
Packagers
Dosage forms
FormRouteStrength
CapsuleOral25 mg, 50 mg, 100 mg
EmulsionOphthalmic0.05%
Injection, solutionIntravenous50 mg/mL
SolutionOral100 mg/mL
Prices
Unit descriptionCostUnit
SandIMMUNE 100 mg/ml Solution 50ml Bottle499.62USDbottle
Neoral 100 mg/ml Solution 50ml Bottle346.14USDbottle
CycloSPORINE Modified 100 mg/ml Solution 50ml Bottle311.53USDbottle
SandIMMUNE 30 100 mg capsule Box308.69USDbox
Restasis 30 0.05% Emulsion 1 Box = 30 Containers205.99USDbox
Neoral 30 100 mg capsule Box190.54USDbox
CycloSPORINE Modified 30 100 mg capsule Box171.48USDbox
Gengraf 30 100 mg capsule Box159.94USDbox
SandIMMUNE 30 25 mg capsule Box77.33USDbox
Neoral 30 25 mg capsule Box47.69USDbox
SandIMMUNE 50 mg/ml Solution 5ml Ampule46.38USDampule
Gengraf 30 25 mg capsule Box42.99USDbox
CycloSPORINE Modified 30 25 mg capsule Box42.9USDbox
Cyclosporine a powder25.2USDg
Sandimmune 100 mg capsule9.89USDcapsule
Sandimmune 50 mg/ml ampul7.71USDml
Cyclosporine 100 mg capsule6.46USDcapsule
Neoral 100 mg gelatn capsule6.11USDcapsule
Cyclosporine 100 mg softgel5.5USDsoftgel capsule
Cyclosporine modif 100 mg softgel5.5USDsoftgel capsule
Cyclosporine modif 100 mg capsule5.49USDcapsule
Cyclosporine 50 mg/ml amp5.45USDml
Cyclosporine 50 mg/ml vial5.28USDml
Gengraf 100 mg capsule5.28USDcapsule
Restasis 0.05% eye emulsion4.49USDeach
Cyclosporine 50 mg softgel2.74USDsoftgel capsule
Sandimmune 25 mg capsule2.48USDcapsule
Cyclosporine 25 mg capsule1.56USDcapsule
Neoral 25 mg gelatin capsule1.53USDcapsule
Cyclosporine 25 mg softgel1.38USDsoftgel capsule
Gengraf 25 mg capsule1.32USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States59853211994-09-262014-09-26
United States48393421992-08-022009-08-02
Canada21080182003-04-152012-04-16
Canada13321501994-09-272011-09-27
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point148-151 °CNot Available
Caco2 permeability-6.05ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00952ALOGPS
logP4.12ALOGPS
logP3.64ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)11.83ChemAxon
pKa (Strongest Basic)-2.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area278.8 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity327.14 m3·mol-1ChemAxon
Polarizability133.24 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Hans Dietl, “Pharmaceutical preparation containing cyclosporine(s) for intravenous administration and a process for its production.” U.S. Patent US5527537, issued October, 1990.

US5527537
General Reference
  1. Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S: Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994 Jun 30;330(26):1841-5. Pubmed
  2. Synthesis Information Link
  3. Pubmed
External Links
ResourceLink
KEGG DrugD00184
KEGG CompoundC05086
ChEBI4031
ChEMBLCHEMBL160
Therapeutic Targets DatabaseDNC001177
PharmGKBPA449167
Drug Product Database593257
RxListhttp://www.rxlist.com/cgi/generic/cyclosporine.htm
Drugs.comhttp://www.drugs.com/cdi/cyclosporine-drops.html
WikipediaCyclosporine
ATC CodesL04AD01S01XA18
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelshow(176 KB)
MSDSshow(83.2 KB)
Interactions
Drug Interactions
Drug
AcetazolamideAcetazolamide may increase the effect and toxicity of cyclosporine.
AliskirenAvoid combination because cyclosporine increases aliskiren serum concentration.
AllopurinolAllopurinol increases the effect and toxicity of cyclosporine
AmiodaroneAmiodarone may increase the therapeutic and adverse effects of cyclosporine.
AmobarbitalThe barbiturate, amobarbital, increases the effect of cyclosporine.
Amphotericin BMonitor for nephrotoxicity
AmprenavirThe protease inhibitor, amprenavir, may increase the effect of cyclosporine.
AprobarbitalThe barbiturate, aprobarbital, increases the effect of cyclosporine.
AtazanavirAtazanavir may increase the therapeutic and adverse effects of cyclosporine.
AtorvastatinPossible myopathy and rhabdomyolysis
AzithromycinThe macrolide, azithromycin, may increase the effect of cyclosporine.
BezafibrateCyclosporine may enhance the nephrotoxic effect of fibric acid derivatives like bezafibrate. Fibric acid derivatives may decrease the serum concentration of cyclosporine. Extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary.
BosentanCyclosporine may increase the effect and toxicity of bosentan.
BupropionBupropion may decrease the therapeutic effect of cyclosporine.
ButabarbitalThe barbiturate, butabarbital, increases the effect of cyclosporine.
ButalbitalThe barbiturate, butalbital, increases the effect of cyclosporine.
ButethalThe barbiturate, butethal, increases the effect of cyclosporine.
CarbamazepineCarbamazepine may decrease the therapeutic effect of cyclosporine.
CarvedilolCarvedilol may increase the therapeutic and adverse effects of cyclosporine.
CaspofunginCyclosporine increases the effect and toxicity of caspofungin
CerivastatinPossible myopathy and rhabdomyolysis
ChloramphenicolChloramphenicol may increase the effect of cyclosporine.
ChloroquineChloroquine may increase the therapeutic and adverse effects of cyclosporine.
CilastatinImipenem increases the effect and toxicity of cyclosporine
CiprofloxacinCiprofloxacin may increase the effect and toxicity of cyclosporine.
ClarithromycinThe macrolide, clarithromycin, may increase the effect of cyclosporine.
ClindamycinClindamycin may decrease the therapeutic effect of cyclosporine.
ColchicineIncreased toxicity of both drugs
DanazolThe androgen, danazol, may increase the effect and toxicity of cyclosporine.
DiclofenacMonitor for nephrotoxicity
DigoxinCyclosporine may increase the effect of digoxin.
Dihydroquinidine barbiturateThe barbiturate, dihydroquinidine barbiturate, increases the effect of cyclosporine.
DiltiazemDiltiazem may increase the effect and toxicity of cyclosporine.
DronedaroneCyclosporine is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
EfavirenzEfavirenz decreases the levels of cyclosporine
ErythromycinThe macrolide, erythromycin, may increase the effect of cyclosporine.
Ethinyl EstradiolThe contraceptive increases the effect and toxicity of cyclosporine
EthotoinThe hydantoin decreases the effect of cyclosporine
EtodolacMonitor for nephrotoxicity
EtoposideCyclosporine may increase the therapeutic and adverse effects of etoposide.
EzetimibeCyclosporine may increase the therapeutic and adverse effects of ezetimibe.
FenoprofenMonitor for nephrotoxicity
FidaxomicinCyclosporin is an inhibitor of p-glycoprotein and concomitant therapy will result in a increase in Cmax and AUC of fidaxomicin and its metabolite.
FluconazoleFluconazole may increase the therapeutic and adverse effects of the cyclosporine.
FluoxetineThe antidepressant increases the effect and toxicity of cyclosporine
FlurbiprofenMonitor for nephrotoxicity
FluvastatinPossible myopathy and rhabdomyolysis
FosamprenavirThe protease inhibitor, fosamprenavir, may increase the effect of cyclosporine.
FoscarnetMonitor for nephrotoxicity
FosphenytoinThe hydantoin decreases the effect of cyclosporine
GlimepirideThe sulfonylurea, glimepiride, may increase the effect of cyclosporine.
GlipizideThe sulfonylurea, glipizide, may increase the effect of cyclosporine.
GlyburideThe sulfonylurea, glibenclamide, may increase the effect of cyclosporine.
GriseofulvinGriseofulvin decreases the effect of cyclosporine
HeptabarbitalThe barbiturate, heptabarbital, increases the effect of cyclosporine.
HexobarbitalThe barbiturate, hexobarbital, increases the effect of cyclosporine.
IbuprofenMonitor for nephrotoxicity
ImatinibImatinib increases the effect and toxicity of cyclosporine
ImipenemImipenem increases the effect and toxicity of cyclosporine
IndinavirThe protease inhibitor, indinavir, may increase the effect of cyclosporine.
IndomethacinMonitor for nephrotoxicity
ItraconazoleItraconazole may increase the effect of cyclosporine.
JosamycinThe macrolide, josamycin, may increase the effect of cyclosporine.
KetoconazoleKetoconazole may increase the effect of cyclosporine.
KetoprofenThe NSAID, ketoprofen, may increase the serum concentration of cyclosporine. Ketoprofen may also increase the nephrotoxicity of cyclosporine.
LovastatinPossible myopathy and rhabdomyolysis
Meclofenamic acidMonitor for nephrotoxicity
Mefenamic acidMonitor for nephrotoxicity
MelphalanMelphalan increases toxicity of cyclosporine
MephenytoinThe hydantoin decreases the effect of cyclosporine
MestranolThe contraceptive increases the effect and toxicity of cyclosporine
MethohexitalThe barbiturate, methohexital, increases the effect of cyclosporine.
MethotrexateCyclosporine may increase the effect and toxicity of methotrexate.
MethylphenidateMethylphenidate increases the effect and toxicity of cyclosporine
MethylphenobarbitalThe barbiturate, methylphenobarbital, increases the effect of cyclosporine.
MetoclopramideMetoclopramide increases serum levels of cyclosporine
ModafinilModafinil decreases the effect of cyclosporine
MuromonabMuromonab increases the levels of cyclosporine
NabumetoneMonitor for nephrotoxicity
NafcillinNafcillin alters serum levels of cyclosporine
NaproxenMonitor for nephrotoxicity
NefazodoneThe antidepressant increases the effect and toxicity of cyclosporine
NelfinavirThe protease inhibitor, nelfinavir, may increase the effect of cyclosporine.
NicardipineNicardipine increases the effect and toxicity of cyclosporine
NifedipineIncreased risk of gingivitis
NorfloxacinNorfloxacin may increase the effect and toxicity of cyclosporine.
OctreotideOctreotide decreases the effect of cyclosporine
OmeprazoleOmeprazole increases the effect and toxicity of cyclosporine
OrlistatOrlistat decreases the effect of cyclosporine
OxaprozinMonitor for nephrotoxicity
OxcarbazepineOxcarbazepine decreases the effect of cyclosporine
PentobarbitalThe barbiturate, pentobarbital, increases the effect of cyclosporine.
PhenobarbitalThe barbiturate, phenobarbital, may decrease the therapeutic effect of cyclosporine by increasing its metabolism.
PhenytoinThe hydantoin decreases the effect of cyclosporine
PiroxicamMonitor for nephrotoxicity
PitavastatinCyclosporine decreases metabolism of pitavastatin thus increasing serum concentration. Avoid concomitant drug therapy.
PosaconazoleIncreased level of cyclosporine
PravastatinPossible myopathy and rhabdomyolysis
PrimidoneThe barbiturate, primidone, increases the effect of cyclosporine.
ProbucolProbucol decreases the effect of cyclosporine
PropafenonePropafenone increases the effect and toxicity of cyclosporine
PyrazinamidePyrazinamide decreases the effect of cyclosporine
Quinidine barbiturateThe barbiturate, quinidine barbiturate, increases the effect of cyclosporine.
QuinupristinSynercid increases the effect of cyclosporine
RepaglinideCyclosporine may increase the therapeutic and adverse effects of repaglinide.
RifabutinThe rifamycin decreases the effect of cyclosporine
RifampicinThe rifamycin decreases the effect of cyclosporine
Rilonaceptresults in increased immunosuppressive effects; increases the risk of infection.
RitonavirThe protease inhibitor, ritonavir, may increase the effect of cyclosporine.
RosuvastatinCyclosporine may increase the serum concentration of rosuvastatin. Limit rosuvastatin dosing to 5 mg/day and monitor for changes in the therapeutic and adverse effects of rosuvastatin if cyclosporine is initiated, discontinued or dose changed.
RoxithromycinThe macrolide, roxithromycin, may increase the effect of cyclosporine.
SaquinavirThe protease inhibitor, saquinavir, may increase the effect of cyclosporine.
SecobarbitalThe barbiturate, secobarbital, increases the effect of cyclosporine.
SevelamerSevelamer decreases the effect of cyclosporine
SibutramineSibutramine increases the effect and toxicity of cyclosporine
SimvastatinPossible myopathy and rhabdomyolysis
SirolimusIncreases the effect and toxicity of sirolimus
St. John's WortSt. John's Wort decreases the effect of cyclosporine
SulfadiazineThe sulfonamide decreases the effect of cyclosporine
SulfamethazineThe sulfonamide decreases the effect of cyclosporine
SulfamethoxazoleThe sulfonamide decreases the effect of cyclosporine
SulfasalazineThe sulfonamide decreases the effect of cyclosporine
SulfinpyrazoneSulfinpyrazone decreases the effect of cyclosporine
SulindacThe NSAID, sulindac, may increase the nephrotoxic effect of cyclosporine. Sulindac may increase the serum concentration of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine levels and nephrotoxicity during concomitant therapy.
TacrolimusAdditive renal impairment may occur during concomitant therapy with cyclosporine. Combination therapy should be avoided.
TalbutalThe sulfonamide decreases the effect of cyclosporine
TamsulosinCyclosporine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cyclosporine is initiated, discontinued, or dose changed.
TelaprevirTelaprevir increases levels by affecting CYP3A4 metabolism. Must monitor levels closely with concomitant therapy.
TelithromycinTelithromycin may reduce clearance of cyclosporine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of cyclosporine if telithromycin is initiated, discontinued or dose changed.
TenoxicamMonitor for nephrotoxicity
TerbinafineTerbinafine may decrease the plasma concentration and therapeutic effect of cyclosporine.
TestolactoneThe androgen, Testolactone, may increase the hepatotoxicity of Cyclosporine. Testolatone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
TestosteroneThe androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
Testosterone PropionateThe androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
ThiopentalThiopental may increase the metabolism and clearance of Cyclosporine. Monitor for changes in the therapeutic/adverse effects of Cyclosporine if Thiopental is initiated, discontinued or dose changed.
Tiaprofenic acidTiaprofenic acid may increase the nephrotoxicity and/or the serum concentration of cyclosporine. Consider altnerate therapy or monitor for increased cyclosporine concentrations and nephrotoxicity during concomitant therapy.
TiclopidineTiclopidine decreases the effect of cyclosporine
TipranavirTipranavir may affect the efficacy/toxicity of Cyclosporine.
TobramycinIncreased risk of nephrotoxicity
TofacitinibCyclosporin (and other strong immunosuppressants), when used in combination with tofacitinib, may increase the risk of added immunosuppression and infection. It is recommended to avoid concurrent therapy.
TolmetinTolmetin may increase the serum concentration of cyclosporine and/or increase the nephrotoxicity of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine serum concentration and nephrotoxicity during concomitant therapy.
TolterodineCyclosporine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TopotecanThe p-glycoprotein inhibitor, Cyclosporine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
TramadolCyclosporine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrandolaprilThe ACE inhibitor, Trandolapril, may increase the nephrotoxicity of Cyclosporine.
transdermal testosterone gelThe androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
TrazodoneThe CYP3A4 inhibitor, Cyclosporine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Cyclosporine is initiated, discontinued or dose changed.
TroglitazoneTroglitazone decreases the effect of the immunosuppressant
TroleandomycinThe macrolide, troleandomycin, may increase the effect of cyclosporine.
Ursodeoxycholic acidUrsodiol increases the levels of cyclosporine
VerapamilVerapamil may increase the serum concentration of cyclosporine by inhibiting CYP3A4-mediated metabolism of cyclosporine. Monitor for changes in the therapeutic/adverse effects of cyclosporine if verapamil is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of cyclosporine by decreasing its metabolism. Consider reducing the dose of cyclosporine. Monitor cyclosporine serum concentrations and therapeutic and toxic effects if initiating, discontinuing or adjusting voriconazole therapy.
Food Interactions
  • Avoid salt substitutes containing potassium.
  • Avoid taking with grapefruit or grapefruit juice as grapefruit can significantly increase serum levels of this product.
  • Red wine may reduce cyclosporine levels due to increased metabolism, therefore it appears prudent to avoid red wine (white wine does not appear to affect cyclosporine metabolism).
  • When taken with a meal, AUC and Cmax of cyclosporine modified decreased.

Targets

1. Calcium signal-modulating cyclophilin ligand

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details
Calcium signal-modulating cyclophilin ligand P49069 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Bernasconi R, Solda T, Galli C, Pertel T, Luban J, Molinari M: Cyclosporine a-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation. PLoS One. 2010 Sep 28;5(9). pii: e13008. Pubmed
  4. Yamashita H, Ito T, Kato H, Asai S, Tanaka H, Nagai H, Inagaki N: Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis. Eur J Pharmacol. 2010 Oct 25;645(1-3):171-6. Epub 2010 Aug 3. Pubmed
  5. Galat A, Bua J: Molecular aspects of cyclophilins mediating therapeutic actions of their ligands. Cell Mol Life Sci. 2010 Oct;67(20):3467-88. Epub 2010 Jul 4. Pubmed
  6. Lee J, Kim SS: Current implications of cyclophilins in human cancers. J Exp Clin Cancer Res. 2010 Jul 19;29:97. Pubmed

2. Calcineurin subunit B type 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Calcineurin subunit B type 2 Q96LZ3 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Yamashita H, Ito T, Kato H, Asai S, Tanaka H, Nagai H, Inagaki N: Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis. Eur J Pharmacol. 2010 Oct 25;645(1-3):171-6. Epub 2010 Aug 3. Pubmed

3. Peptidyl-prolyl cis-trans isomerase A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Peptidyl-prolyl cis-trans isomerase A P62937 Details

References:

  1. Keckesova Z, Ylinen LM, Towers GJ: Cyclophilin A renders human immunodeficiency virus type 1 sensitive to Old World monkey but not human TRIM5 alpha antiviral activity. J Virol. 2006 May;80(10):4683-90. Pubmed
  2. Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM: The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11393-8. Epub 2006 Jul 18. Pubmed
  3. Redell JB, Zhao J, Dash PK: Acutely increased cyclophilin a expression after brain injury: a role in blood-brain barrier function and tissue preservation. J Neurosci Res. 2007 Jul;85(9):1980-8. Pubmed
  4. Schaller T, Ylinen LM, Webb BL, Singh S, Towers GJ: Fusion of cyclophilin A to Fv1 enables cyclosporine-sensitive restriction of human and feline immunodeficiency viruses. J Virol. 2007 Sep;81(18):10055-63. Epub 2007 Jul 3. Pubmed
  5. Lee J, Kim SS: Current implications of cyclophilins in human cancers. J Exp Clin Cancer Res. 2010 Jul 19;29:97. Pubmed
  6. Stegmann CM, Luhrmann R, Wahl MC: The crystal structure of PPIL1 bound to cyclosporine A suggests a binding mode for a linear epitope of the SKIP protein. PLoS One. 2010 Apr 2;5(4):e10013. Pubmed

4. Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Peptidyl-prolyl cis-trans isomerase F, mitochondrial P30405 Details

References:

  1. Handschumacher RE, Harding MW, Rice J, Drugge RJ, Speicher DW: Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544-7. Pubmed

Enzymes

1. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed
  4. Lexicomp.

4. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Lexicomp

7. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. Pubmed
  2. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. Pubmed
  3. Tiberghien F, Kurome T, Takesako K, Didier A, Wenandy T, Loor F: Aureobasidins: structure-activity relationships for the inhibition of the human MDR1 P-glycoprotein ABC-transporter. J Med Chem. 2000 Jun 29;43(13):2547-56. Pubmed
  4. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. Pubmed
  5. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  6. Leonessa F, Kim JH, Ghiorghis A, Kulawiec RJ, Hammer C, Talebian A, Clarke R: C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pump. J Med Chem. 2002 Jan 17;45(2):390-8. Pubmed
  7. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. Pubmed
  8. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. Pubmed
  9. Kumar S, Kwei GY, Poon GK, Iliff SA, Wang Y, Chen Q, Franklin RB, Didolkar V, Wang RW, Yamazaki M, Chiu SH, Lin JH, Pearson PG, Baillie TA: Pharmacokinetics and interactions of a novel antagonist of chemokine receptor 5 (CCR5) with ritonavir in rats and monkeys: role of CYP3A and P-glycoprotein. J Pharmacol Exp Ther. 2003 Mar;304(3):1161-71. Pubmed
  10. Horie K, Tang F, Borchardt RT: Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res. 2003 Feb;20(2):161-8. Pubmed
  11. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. Pubmed
  12. Atkinson DE, Greenwood SL, Sibley CP, Glazier JD, Fairbairn LJ: Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. Am J Physiol Cell Physiol. 2003 Sep;285(3):C584-91. Epub 2003 Apr 30. Pubmed
  13. Hamada A, Miyano H, Watanabe H, Saito H: Interaction of imatinib mesilate with human P-glycoprotein. J Pharmacol Exp Ther. 2003 Nov;307(2):824-8. Epub 2003 Sep 15. Pubmed
  14. Corea G, Fattorusso E, Lanzotti V, Taglialatela-Scafati O, Appendino G, Ballero M, Simon PN, Dumontet C, Di Pietro A: Modified jatrophane diterpenes as modulators of multidrug resistance from Euphorbia dendroides L. Bioorg Med Chem. 2003 Nov 17;11(23):5221-7. Pubmed
  15. Rao US, Scarborough GA: Direct demonstration of high affinity interactions of immunosuppressant drugs with the drug binding site of the human P-glycoprotein. Mol Pharmacol. 1994 Apr;45(4):773-6. Pubmed
  16. Pouliot JF, L’Heureux F, Liu Z, Prichard RK, Georges E: Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem Pharmacol. 1997 Jan 10;53(1):17-25. Pubmed
  17. Kuhnel JM, Perrot JY, Faussat AM, Marie JP, Schwaller MA: Functional assay of multidrug resistant cells using JC-1, a carbocyanine fluorescent probe. Leukemia. 1997 Jul;11(7):1147-55. Pubmed
  18. Ito T, Yano I, Tanaka K, Inui KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther. 1997 Aug;282(2):955-60. Pubmed
  19. Kim AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45. Pubmed
  20. Kusunoki N, Takara K, Tanigawara Y, Yamauchi A, Ueda K, Komada F, Ku Y, Kuroda Y, Saitoh Y, Okumura K: Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein. Jpn J Cancer Res. 1998 Nov;89(11):1220-8. Pubmed
  21. Golstein PE, Boom A, van Geffel J, Jacobs P, Masereel B, Beauwens R: P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers Arch. 1999 Apr;437(5):652-60. Pubmed
  22. Wigler PW: PSC833, cyclosporin A, and dexniguldipine effects on cellular calcein retention and inhibition of the multidrug resistance pump in human leukemic lymphoblasts. Biochem Biophys Res Commun. 1999 Apr 13;257(2):410-3. Pubmed
  23. Hochman JH, Chiba M, Nishime J, Yamazaki M, Lin JH: Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther. 2000 Jan;292(1):310-8. Pubmed
  24. Asakura E, Nakayama H, Sugie M, Zhao YL, Nadai M, Kitaichi K, Shimizu A, Miyoshi M, Takagi K, Takagi K, Hasegawa T: Azithromycin reverses anticancer drug resistance and modifies hepatobiliary excretion of doxorubicin in rats. Eur J Pharmacol. 2004 Jan 26;484(2-3):333-9. Pubmed
  25. D’Emanuele A, Jevprasesphant R, Penny J, Attwood D: The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J Control Release. 2004 Mar 24;95(3):447-53. Pubmed
  26. Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. Pubmed
  27. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
  28. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. Pubmed
  29. Kugawa F, Suzuki T, Miyata M, Tomono K, Tamanoi F: Construction of a model cell line for the assay of MDR1 (multi drug resistance gene-1) substrates/inhibitors using HeLa cells. Pharmazie. 2009 May;64(5):296-300. Pubmed
  30. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. Epub 2009 Mar 25. Pubmed
  31. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  32. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. Pubmed
  33. Seeballuck F, Ashford MB, O’Driscoll CM: The effects of pluronics block copolymers and Cremophor EL on intestinal lipoprotein processing and the potential link with P-glycoprotein in Caco-2 cells. Pharm Res. 2003 Jul;20(7):1085-92. Pubmed
  34. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
  35. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T: Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem. 1993 Mar 25;268(9):6077-80. Pubmed
  36. Fricker G, Drewe J, Huwyler J, Gutmann H, Beglinger C: Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: in vitro-in vivo correlation. Br J Pharmacol. 1996 Aug;118(7):1841-7. Pubmed
  37. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ, Watkins PB: Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther. 1997 Sep;62(3):248-60. Pubmed
  38. Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA, Benet LZ: Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res. 1999 Apr;16(4):478-85. Pubmed
  39. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed

2. Canalicular multispecific organic anion transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 2 O15438 Details

References:

  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. Pubmed

3. Bile salt export pump

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Bile salt export pump O95342 Details

References:

  1. Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ: The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002 Nov;123(5):1649-58. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
  3. Noe J, Hagenbuch B, Meier PJ, St-Pierre MV: Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Hepatology. 2001 May;33(5):1223-31. Pubmed
  4. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. Pubmed
  5. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000 Feb;118(2):422-30. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Pec MK, Aguirre A, Fernandez JJ, Souto ML, Dorta JF, Villar J: Dehydrothyrsiferol does not modulate multidrug resistance-associated protein 1 resistance: a functional screening system for MRP1 substrates. Int J Mol Med. 2002 Nov;10(5):605-8. Pubmed
  2. Leier I, Jedlitschky G, Buchholz U, Cole SP, Deeley RG, Keppler D: The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem. 1994 Nov 11;269(45):27807-10. Pubmed

5. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. Pubmed

6. Ileal sodium/bile acid cotransporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Ileal sodium/bile acid cotransporter Q12908 Details

References:

  1. Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA: Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69. Pubmed

7. Sodium/bile acid cotransporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium/bile acid cotransporter Q14973 Details

References:

  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. Pubmed

8. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Sweet DH, Wolff NA, Pritchard JB: Expression cloning and characterization of ROAT1. The basolateral organic anion transporter in rat kidney. J Biol Chem. 1997 Nov 28;272(48):30088-95. Pubmed

9. Multidrug resistance-associated protein 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 7 Q5T3U5 Details

References:

  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. Pubmed

10. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. Pubmed
  2. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. Pubmed
  3. Kamisako T, Leier I, Cui Y, Konig J, Buchholz U, Hummel-Eisenbeiss J, Keppler D: Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology. 1999 Aug;30(2):485-90. Pubmed
  4. Chen ZS, Kawabe T, Ono M, Aoki S, Sumizawa T, Furukawa T, Uchiumi T, Wada M, Kuwano M, Akiyama SI: Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter. Mol Pharmacol. 1999 Dec;56(6):1219-28. Pubmed
  5. Horikawa M, Kato Y, Tyson CA, Sugiyama Y: The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet. 2002;17(1):23-33. Pubmed

11. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. Pubmed

12. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. Pubmed
  2. Shitara Y, Itoh T, Sato H, Li AP, Sugiyama Y: Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J Pharmacol Exp Ther. 2003 Feb;304(2):610-6. Pubmed
  3. Nozawa T, Tamai I, Sai Y, Nezu J, Tsuji A: Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin. J Pharm Pharmacol. 2003 Jul;55(7):1013-20. Pubmed
  4. Fehrenbach T, Cui Y, Faulstich H, Keppler D: Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn Schmiedebergs Arch Pharmacol. 2003 Nov;368(5):415-20. Epub 2003 Oct 3. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08