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Identification
NameCapecitabine
Accession NumberDB01101  (APRD00203)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.

Structure
Thumb
Synonyms
SynonymLanguageCode
(1-(5-Deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-carbamic acid pentyl esterNot AvailableNot Available
CapecitabinNot AvailableNot Available
CapecitabinaNot AvailableNot Available
CapecitabinumNot AvailableNot Available
Pentyl [1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamateNot AvailableNot Available
Pentyl 1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamateNot AvailableNot Available
XelodaNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Xelodatablet, film coated150 mgoralGenentech, Inc.1998-04-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Xelodatablet, film coated500 mgoralGenentech, Inc.1998-04-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Xelodatablet, film coated500 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Xelodatablet, film coated150 mgoralPhysicians Total Care, Inc.2005-02-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Xelodatablet, film coated500 mgoralPhysicians Total Care, Inc.2005-06-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Xelodatablet150 mgoralHoffmann La Roche LimitedNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Xelodatablet500 mgoralHoffmann La Roche LimitedNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Capecitabinetablet, film coated150 mgoralTeva Pharmaceuticals USA Inc2014-03-07Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Capecitabinetablet, film coated500 mgoralTeva Pharmaceuticals USA Inc2014-03-07Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Capecitabinetablet, film coated500 mgoralKAISER FOUNDATION HOSPITALS2014-05-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Capecitabinetablet, film coated150 mgoralMylan Pharmaceuticals Inc.2014-08-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Capecitabinetablet, film coated500 mgoralMylan Pharmaceuticals Inc.2014-08-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Capecitabinetablet, film coated500 mgoralMylan Institutional Inc.2014-08-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number154361-50-9
WeightAverage: 359.3501
Monoisotopic: 359.149263656
Chemical FormulaC15H22FN3O6
InChI KeyGAGWJHPBXLXJQN-UORFTKCHSA-N
InChI
InChI=1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1
IUPAC Name
pentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate
SMILES
CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as glycosylamines. These are compounds consisting of an amine with a beta-N-glycosidic bond to a carbohydrate, thus forming a cyclic hemiaminal ether bond (alpha-amino ether).
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassGlycosyl compounds
Direct ParentGlycosylamines
Alternative Parents
Substituents
  • N-glycosyl compound
  • Pyrimidone
  • Halopyrimidine
  • Aminopyrimidine
  • Imidolactam
  • Pyrimidine
  • Hydropyrimidine
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Oxolane
  • Secondary alcohol
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. May also be used in combination with docetaxel for the treatment of metastatic breast cancer in patients who have failed to respond to, or recurred or relasped during or following anthracycline-containing chemotherapy. Capecitabine is used alone as an adjuvant therapy following the complete resection of primary tumor in patients with stage III colon cancer when monotherapy with fluroprymidine is preferred. The use or capecitabine in combination regimens for advanced gastric cancer is currently being investigated.
PharmacodynamicsCapecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).
Mechanism of actionCapecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, therefore a deficiency of this compound can inhibit cell division. Secondly, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis through the production of fraudulent RNA.
AbsorptionReadily absorbed through the GI tract (~70%)
Volume of distributionNot Available
Protein binding< 60% (mainly albumin)
Metabolism

Metabolized by thymidine phosphorylase to fluoruracil.

SubstrateEnzymesProduct
Capecitabine
5’-Deoxy-5-fluorouridineDetails
5’-Deoxy-5-fluorouridine
5-fluorouracilDetails
Route of eliminationCapecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug.
Half life45-60 minutes for capecitabine and its metabolites.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Capecitabine Action PathwayDrug actionSMP00469
Capecitabine Metabolism PathwayDrug metabolismSMP00607
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9513
Blood Brain Barrier+0.6064
Caco-2 permeable-0.7096
P-glycoprotein substrateSubstrate0.5106
P-glycoprotein inhibitor INon-inhibitor0.8234
P-glycoprotein inhibitor IINon-inhibitor0.7514
Renal organic cation transporterNon-inhibitor0.9654
CYP450 2C9 substrateNon-substrate0.7999
CYP450 2D6 substrateNon-substrate0.864
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.7523
CYP450 2C9 substrateNon-inhibitor0.7673
CYP450 2D6 substrateNon-inhibitor0.8612
CYP450 2C19 substrateNon-inhibitor0.6569
CYP450 3A4 substrateNon-inhibitor0.7404
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8484
Ames testNon AMES toxic0.6521
CarcinogenicityNon-carcinogens0.8754
BiodegradationNot ready biodegradable0.9964
Rat acute toxicity2.4690 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9759
hERG inhibition (predictor II)Non-inhibitor0.7124
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral150 mg
Tabletoral500 mg
Tablet, film coatedoral150 mg
Tablet, film coatedoral500 mg
Prices
Unit descriptionCostUnit
Xeloda 500 mg tablet28.97USD tablet
Xeloda 150 mg tablet8.69USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada13273581994-03-012011-03-01
Canada21033241997-12-232013-11-17
United States49668911994-01-132011-01-13
United States54729491993-12-142013-12-14
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point110-121 °CNot Available
water solubility26 mg/mLNot Available
logP0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.248 mg/mLALOGPS
logP1.17ALOGPS
logP0.77ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)8.23ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area120.69 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity82.75 m3·mol-1ChemAxon
Polarizability35.81 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5472949
General Reference
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed
  2. Wagstaff AJ, Ibbotson T, Goa KL: Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63(2):217-36. Pubmed
  3. Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J: Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules. 2008 Aug 27;13(8):1897-922. Pubmed
  4. Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. Pubmed
  5. Milano G, Ferrero JM, Francois E: Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation. Br J Cancer. 2004 Aug 16;91(4):613-7. Pubmed
  6. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed
External Links
ATC CodesL01BC06
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (133 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolMay increase the serum concentration of Vitamin K Antagonists.
BosentanCYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan.
CarvedilolCYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased.
CimetidineCimetidine may increase serum concentrations of the active metabolite(s) of Capecitabine. Specifically, concentrations of fluorouracil may be increased.
ClozapineMyelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased.
DenosumabMay enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
DronabinolCYP2C9 Inhibitors (Strong) may increase the serum concentration of Dronabinol.
FosphenytoinCapecitabine may increase the serum concentration of Fosphenytoin.
LacosamideCYP2C9 Inhibitors (Strong) may increase the serum concentration of Lacosamide.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
NatalizumabImmunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
OspemifeneCYP2C9 Inhibitors (Strong) may increase the serum concentration of Ospemifene.
PhenytoinMay increase the serum concentration of Phenytoin.
PimecrolimusMay enhance the adverse/toxic effect of Immunosuppressants.
RoflumilastMay enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-TImmunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
TofacitinibImmunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
TrastuzumabMay enhance the neutropenic effect of Immunosuppressants.
Food Interactions
  • Take 12 hours apart, within 30 minutes of the end of breakfast and dinner to reduce nausea.

Targets

1. Thymidylate synthase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Thymidylate synthase P04818 Details

References:

  1. Patel A, Pluim T, Helms A, Bauer A, Tuttle RM, Francis GL: Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults. Cancer Chemother Pharmacol. 2004 May;53(5):409-14. Pubmed
  2. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. Pubmed
  3. Carlini LE, Meropol NJ, Bever J, Andria ML, Hill T, Gold P, Rogatko A, Wang H, Blanchard RL: UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36. Pubmed
  4. Li KM, Rivory LP, Clarke SJ: Rapid quantitation of plasma 2’-deoxyuridine by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry and its application to pharmacodynamic studies in cancer patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jun 5;820(1):121-30. Epub 2005 Apr 19. Pubmed
  5. Fischel JL, Ciccolini J, Formento P, Ferrero JM, Milano G: Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5’-deoxyuridine. Anticancer Drugs. 2006 Aug;17(7):807-13. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: incorporation into and destabilization

Components

Name UniProt ID Details

References:

  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed
  2. Thomas DM, Zalcberg JR: 5-fluorouracil: a pharmacological paradigm in the use of cytotoxics. Clin Exp Pharmacol Physiol. 1998 Nov;25(11):887-95. Pubmed
  3. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. Pubmed
  4. Ghoshal K, Jacob ST: An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol. 1997 Jun 1;53(11):1569-75. Pubmed
  5. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. Pubmed
  6. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. Pubmed

3. RNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: incorporation into and destabilization

Components

Name UniProt ID Details

References:

  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed
  2. Thomas DM, Zalcberg JR: 5-fluorouracil: a pharmacological paradigm in the use of cytotoxics. Clin Exp Pharmacol Physiol. 1998 Nov;25(11):887-95. Pubmed
  3. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. Pubmed
  4. Ghoshal K, Jacob ST: An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol. 1997 Jun 1;53(11):1569-75. Pubmed
  5. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. Pubmed
  6. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. Pubmed

Enzymes

1. Thymidine phosphorylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Thymidine phosphorylase P19971 Details

References:

  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed
  2. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y: A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202. Pubmed
  3. Blanquicett C, Gillespie GY, Nabors LB, Miller CR, Bharara S, Buchsbaum DJ, Diasio RB, Johnson MR: Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45. Pubmed
  4. Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine] Yakugaku Zasshi. 1999 Dec;119(12):881-97. Pubmed
  5. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. Pubmed
  6. Endo M, Miwa M, Eda H, Ura M, Tanimura H, Ishikawa T, Miyazaki-Nose T, Hattori K, Shimma N, Yamada-Okabe H, Ishitsuka H: Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805. Pubmed
  7. Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B: Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45(4):291-7. Pubmed
  8. Patel A, Pluim T, Helms A, Bauer A, Tuttle RM, Francis GL: Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults. Cancer Chemother Pharmacol. 2004 May;53(5):409-14. Pubmed
  9. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. Pubmed
  10. Fischel JL, Ciccolini J, Formento P, Ferrero JM, Milano G: Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5’-deoxyuridine. Anticancer Drugs. 2006 Aug;17(7):807-13. Pubmed
  11. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed
  12. Ranieri G, Roccaro AM, Vacca A, Ribatti D: Thymidine phosphorylase (platelet-derived endothelial cell growth factor) as a target for capecitabine: from biology to the bedside. Recent Pat Anticancer Drug Discov. 2006 Jun;1(2):171-83. Pubmed

2. Liver carboxylesterase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Liver carboxylesterase 1 P23141 Details

References:

  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed
  2. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y: A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202. Pubmed
  3. Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine] Yakugaku Zasshi. 1999 Dec;119(12):881-97. Pubmed
  4. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. Pubmed
  5. Endo M, Miwa M, Eda H, Ura M, Tanimura H, Ishikawa T, Miyazaki-Nose T, Hattori K, Shimma N, Yamada-Okabe H, Ishitsuka H: Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805. Pubmed

3. Dihydropyrimidine dehydrogenase [NADP(+)]

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Dihydropyrimidine dehydrogenase [NADP(+)] Q12882 Details

References:

  1. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y: A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202. Pubmed
  2. Blanquicett C, Gillespie GY, Nabors LB, Miller CR, Bharara S, Buchsbaum DJ, Diasio RB, Johnson MR: Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45. Pubmed
  3. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed
  4. Gross E, Seck K, Neubauer S, Mayr J, Hellebrand H, Ratanaphan A, Lutz V, Stockinger H, Kiechle M: High-throughput genotyping by DHPLC of the dihydropyrimidine dehydrogenase gene implicated in (fluoro)pyrimidine catabolism. Int J Oncol. 2003 Feb;22(2):325-32. Pubmed
  5. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. Pubmed
  6. Endo M, Miwa M, Eda H, Ura M, Tanimura H, Ishikawa T, Miyazaki-Nose T, Hattori K, Shimma N, Yamada-Okabe H, Ishitsuka H: Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805. Pubmed
  7. Patel A, Pluim T, Helms A, Bauer A, Tuttle RM, Francis GL: Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults. Cancer Chemother Pharmacol. 2004 May;53(5):409-14. Pubmed
  8. Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8. Pubmed
  9. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed

4. Cytidine deaminase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytidine deaminase P32320 Details

References:

  1. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed
  2. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y: A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202. Pubmed
  3. Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine] Yakugaku Zasshi. 1999 Dec;119(12):881-97. Pubmed
  4. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54. Pubmed
  5. Endo M, Miwa M, Eda H, Ura M, Tanimura H, Ishikawa T, Miyazaki-Nose T, Hattori K, Shimma N, Yamada-Okabe H, Ishitsuka H: Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805. Pubmed

5. 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

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:22