Identification

Name
Dalfopristin
Accession Number
DB01764  (EXPT01246)
Type
Small Molecule
Groups
Approved
Description

Dalfopristin is a combination of two antibiotics (Dalfopristin and quinupristin) used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. It is not effective against Enterococcus faecalis infections. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis.

Structure
Thumb
Synonyms
  • Dalfopristina
  • Dalfopristine
  • Dalfopristinum
External IDs
RP 54476 / RP-54476
Product Ingredients
IngredientUNIICASInChI Key
Dalfopristin mesylateR5U9EZY06GNot AvailableZUBXFMSQBHKVNC-ODOOVVHSSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SynercidDalfopristin (350 mg) + Quinupristin (150 mg)Powder, for solutionIntravenousMonarch Pharmaceuticals, Inc.2000-07-052008-05-28Canada
SynercidDalfopristin (350 mg/5mL) + Quinupristin (150 mg/5mL)Injection, powder, lyophilized, for solutionIntravenousPfizer Laboratories Div Pfizer Inc.1999-09-21Not applicableUs
Categories
UNII
R9M4FJE48E
CAS number
112362-50-2
Weight
Average: 690.847
Monoisotopic: 690.329849908
Chemical Formula
C34H50N4O9S
InChI Key
SUYRLXYYZQTJHF-VMBLUXKRSA-N
InChI
InChI=1S/C34H50N4O9S/c1-7-37(8-2)16-17-48(44,45)28-13-15-38-31(28)34(43)47-32(22(3)4)24(6)11-12-29(41)35-14-9-10-23(5)18-25(39)19-26(40)20-30-36-27(21-46-30)33(38)42/h9-12,18,21-22,24-25,28,31-32,39H,7-8,13-17,19-20H2,1-6H3,(H,35,41)/b10-9+,12-11+,23-18+/t24-,25-,28-,31-,32-/m1/s1
IUPAC Name
(6R,7S,10R,11R,12E,17E,19E,21S)-6-[2-(diethylamino)ethanesulfonyl]-21-hydroxy-11,19-dimethyl-10-(propan-2-yl)-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0³,⁷]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14,23-tetrone
SMILES
[H]\C1=C(\[H])/C(/C)=C([H])/[[email protected]@]([H])(O)CC(=O)CC2=NC(=CO2)C(=O)N2CC[[email protected]]([H])([[email protected]]2([H])C(=O)O[[email protected]]([H])(C(C)C)[[email protected]]([H])(C)\C([H])=C([H])\C(O)=NC1)S(=O)(=O)CCN(CC)CC

Pharmacology

Indication

For the treatment of bacterial infections (usually in combination with quinupristin).

Structured Indications
Pharmacodynamics

Dalfopristin is a streptogramin antibiotic, derived from pristinamycin IIA.

Mechanism of action

The site of action of dalfopristin is the bacterial ribosome. Dalfopristin has been shown to inhibit the early phase of protein synthesis.

TargetActionsOrganism
AStreptogramin A acetyltransferase
inhibitor
Enterococcus faecium
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Moderate

Metabolism

Converted to an active non-conjugated metabolite by hydrolysis.

Route of elimination
Not Available
Half life

The elimination half-life is approximately 0.70 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
  • Enterococcus faecalis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AtorvastatinThe risk or severity of adverse effects can be increased when Dalfopristin is combined with Atorvastatin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Dalfopristin.Investigational
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Dalfopristin.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Dalfopristin.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Dalfopristin.Withdrawn
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Dalfopristin.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Dalfopristin.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Dalfopristin.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Dalfopristin.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Dalfopristin.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Dalfopristin.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Dalfopristin.Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Dalfopristin.Approved, Investigational
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Dalfopristin.Approved, Investigational
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Dalfopristin.Illicit, Investigational, Withdrawn
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Dalfopristin.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Dalfopristin.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Dalfopristin.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Dalfopristin.Experimental
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Dalfopristin.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Dalfopristin.Approved, Investigational, Vet Approved, Withdrawn
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Dalfopristin.Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Dalfopristin.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Dalfopristin.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Dalfopristin.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Dalfopristin.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Dalfopristin.Experimental
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Dalfopristin.Approved, Experimental
Food Interactions
Not Available

References

General References
  1. Allington DR, Rivey MP: Quinupristin/dalfopristin: a therapeutic review. Clin Ther. 2001 Jan;23(1):24-44. [PubMed:11219478]
  2. Lamb HM, Figgitt DP, Faulds D: Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections. Drugs. 1999 Dec;58(6):1061-97. [PubMed:10651391]
  3. Manzella JP: Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am Fam Physician. 2001 Dec 1;64(11):1863-6. [PubMed:11764864]
  4. Paradisi F, Corti G, Messeri D: Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. Med Clin North Am. 2001 Jan;85(1):1-17. [PubMed:11190346]
External Links
KEGG Drug
D00853
KEGG Compound
C08033
PubChem Compound
6323289
PubChem Substance
46506561
ChemSpider
16736919
ChEMBL
CHEMBL1200937
Therapeutic Targets Database
DAP001294
PharmGKB
PA164746234
HET
DOL
Wikipedia
Dalfopristin
PDB Entries
1mrl / 1sm1 / 2z2p / 4u24 / 4u26
FDA label
Download (67.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
3TerminatedTreatmentInfections, Gram-Positive Bacterial1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous
Powder, for solutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0716 mg/mLALOGPS
logP2.57ALOGPS
logP1.58ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)11.38ChemAxon
pKa (Strongest Basic)7.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area176.42 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity182.84 m3·mol-1ChemAxon
Polarizability72.94 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6544
Blood Brain Barrier-0.9286
Caco-2 permeable-0.6574
P-glycoprotein substrateSubstrate0.7988
P-glycoprotein inhibitor INon-inhibitor0.6395
P-glycoprotein inhibitor IINon-inhibitor0.9399
Renal organic cation transporterNon-inhibitor0.9011
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8118
CYP450 2C9 inhibitorNon-inhibitor0.7261
CYP450 2D6 inhibitorNon-inhibitor0.8606
CYP450 2C19 inhibitorNon-inhibitor0.6834
CYP450 3A4 inhibitorNon-inhibitor0.7363
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9392
Ames testNon AMES toxic0.6184
CarcinogenicityNon-carcinogens0.6071
BiodegradationNot ready biodegradable0.6975
Rat acute toxicity2.6096 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9396
hERG inhibition (predictor II)Non-inhibitor0.7254
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolide lactams
Sub Class
Not Available
Direct Parent
Macrolide lactams
Alternative Parents
Alpha amino acid esters / Macrolactams / 2-heteroaryl carboxamides / Tertiary carboxylic acid amides / Heteroaromatic compounds / Sulfones / Oxazoles / Pyrrolidines / Lactones / Lactams
show 11 more
Substituents
Macrolide lactam / Alpha-amino acid ester / Macrolactam / Alpha-amino acid or derivatives / 2-heteroaryl carboxamide / Azole / Heteroaromatic compound / Oxazole / Pyrrolidine / Sulfone
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Enterococcus faecium
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring acyl groups
Specific Function
Inactivates the A compounds of streptogramin antibiotics by acetylation, thus providing resistance to these antibiotics.
Gene Name
vatD
Uniprot ID
P50870
Uniprot Name
Streptogramin A acetyltransferase
Molecular Weight
23649.22 Da
References
  1. Manfredi R, Sabbatani S: Novel pharmaceutical molecules against emerging resistant gram-positive cocci. Braz J Infect Dis. 2010 Jan-Feb;14(1):96-108. [PubMed:20428664]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Rubinstein E, Prokocimer P, Talbot GH: Safety and tolerability of quinupristin/dalfopristin: administration guidelines. J Antimicrob Chemother. 1999 Sep;44 Suppl A:37-46. [PubMed:10511396]
  2. Lamb HM, Figgitt DP, Faulds D: Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections. Drugs. 1999 Dec;58(6):1061-97. [PubMed:10651391]
  3. Bearden DT: Clinical pharmacokinetics of quinupristin/dalfopristin. Clin Pharmacokinet. 2004;43(4):239-52. [PubMed:15005638]
  4. Delgado G Jr, Neuhauser MM, Bearden DT, Danziger LH: Quinupristin-dalfopristin: an overview. Pharmacotherapy. 2000 Dec;20(12):1469-85. [PubMed:11130220]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 03:04