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

Similar Structures

Synonyms

Dalfopristin
Dalfopristina
Dalfopristine
Dalfopristinum

External IDs

RP 54476 / RP-54476

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Dalfopristin mesylate	R5U9EZY06G	Not Available	ZUBXFMSQBHKVNC-ODOOVVHSSA-N

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Synercid	Dalfopristin (350 mg/5mL) + Quinupristin (150 mg/5mL)	Injection, powder, lyophilized, for solution	Intravenous	Pfizer Laboratories Div Pfizer Inc	1999-09-21	Not applicable
Synercid	Dalfopristin (420 mg/6mL) + Quinupristin (180 mg/6mL)	Injection	Intravenous	Monarch Pharmaceuticals, Inc.	2006-11-22	2006-11-22
Synercid	Dalfopristin (350 mg) + Quinupristin (150 mg)	Powder, for solution	Intravenous	Monarch Pharmaceuticals, Inc.	2000-07-05	2008-05-28

Categories

UNII

R9M4FJE48E

CAS number

112362-50-2

Weight

Average: 690.85
Monoisotopic: 690.32985038

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[23.2.1.0^{3,7}]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14,23-tetrone

SMILES

CCN(CC)CCS(=O)(=O)[C@@H]1CCN2[C@H]1C(=O)O[C@H](C(C)C)[C@H](C)\C=C\C(=O)NC\C=C\C(\C)=C\[C@@H](O)CC(=O)CC1=NC(=CO1)C2=O

Pharmacology

Indication

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

Associated Conditions

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.

Target	Actions	Organism
AStreptogramin A acetyltransferase	inhibitor	Enterococcus faecium

Unlock Additional Data

Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more

Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more

Additional Data Available

Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more

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

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
(R)-warfarin	The serum concentration of (R)-warfarin can be increased when it is combined with Dalfopristin.
(S)-Warfarin	The serum concentration of (S)-Warfarin can be increased when it is combined with Dalfopristin.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be decreased when combined with Dalfopristin.
9-aminocamptothecin	The metabolism of 9-aminocamptothecin can be decreased when combined with Dalfopristin.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Dalfopristin.
Albendazole	The metabolism of Albendazole can be decreased when combined with Dalfopristin.
Alfentanil	The metabolism of Alfentanil can be decreased when combined with Dalfopristin.
Alfuzosin	The metabolism of Alfuzosin can be decreased when combined with Dalfopristin.
Allylestrenol	The metabolism of Allylestrenol can be decreased when combined with Dalfopristin.
Alpelisib	The metabolism of Alpelisib can be decreased when combined with Dalfopristin.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

Learn more

Severity

A severity rating for each drug interaction, from minor to major.

Learn more

Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

Learn more

Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

Learn more

Food Interactions

Not Available

References

General References

Allington DR, Rivey MP: Quinupristin/dalfopristin: a therapeutic review. Clin Ther. 2001 Jan;23(1):24-44. [PubMed:11219478]
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]
Manzella JP: Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am Fam Physician. 2001 Dec 1;64(11):1863-6. [PubMed:11764864]
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

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Osteomyelitis	1
3	Terminated	Treatment	Infections, Gram-Positive Bacterial	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Injection	Intravenous
Injection, powder, lyophilized, for solution	Intravenous
Powder, for solution	Intravenous

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0716 mg/mL	ALOGPS
logP	2.57	ALOGPS
logP	1.58	ChemAxon
logS	-4	ALOGPS
pKa (Strongest Acidic)	13.17	ChemAxon
pKa (Strongest Basic)	7.09	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	9	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	176.42 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	182.84 m³·mol^-1	ChemAxon
Polarizability	72.41 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.6544
Blood Brain Barrier	-	0.9286
Caco-2 permeable	-	0.6574
P-glycoprotein substrate	Substrate	0.7988
P-glycoprotein inhibitor I	Non-inhibitor	0.6395
P-glycoprotein inhibitor II	Non-inhibitor	0.9399
Renal organic cation transporter	Non-inhibitor	0.9011
CYP450 2C9 substrate	Non-substrate	0.7897
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Non-substrate	0.5
CYP450 1A2 substrate	Non-inhibitor	0.8118
CYP450 2C9 inhibitor	Non-inhibitor	0.7261
CYP450 2D6 inhibitor	Non-inhibitor	0.8606
CYP450 2C19 inhibitor	Non-inhibitor	0.6834
CYP450 3A4 inhibitor	Non-inhibitor	0.7363
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9392
Ames test	Non AMES toxic	0.6184
Carcinogenicity	Non-carcinogens	0.6071
Biodegradation	Not ready biodegradable	0.6975
Rat acute toxicity	2.6096 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9396
hERG inhibition (predictor II)	Non-inhibitor	0.7254

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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

Details1. Streptogramin A acetyltransferase

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

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

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
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

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]
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]
Bearden DT: Clinical pharmacokinetics of quinupristin/dalfopristin. Clin Pharmacokinet. 2004;43(4):239-52. [PubMed:15005638]
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 January 21, 2020 16:37

Dalfopristin

Identification

Structure for Dalfopristin (DB01764)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Enzymes

References