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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyDalfopristin
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
Structure for DB01764 (Dalfopristin)
- Synonyms
- 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) + Quinupristin (150 mg) Powder, for solution Intravenous Monarch Pharmaceuticals, Inc. 2000-07-05 2008-05-28 Canada 
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 US 
- 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])/[C@@]([H])(O)CC(=O)CC2=NC(=CO2)C(=O)N2CC[C@]([H])([C@]2([H])C(=O)O[C@]([H])(C(C)C)[C@]([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).
- 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 inhibitorEnterococcus 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
Drug Interaction Drug group Asunaprevir The serum concentration of Asunaprevir can be increased when it is combined with Dalfopristin. Approved, Investigational, Withdrawn Atorvastatin The risk or severity of adverse effects can be increased when Dalfopristin is combined with Atorvastatin. Approved BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Dalfopristin. Investigational Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Dalfopristin. Approved Bromocriptine The risk or severity of adverse effects can be increased when Bromocriptine is combined with Dalfopristin. Approved, Investigational Cabergoline The risk or severity of adverse effects can be increased when Cabergoline is combined with Dalfopristin. Approved Cerivastatin The serum concentration of Cerivastatin can be increased when it is combined with Dalfopristin. Approved, Withdrawn Dihydroergocornine The risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Dalfopristin. Approved Dihydroergocristine The risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Dalfopristin. Approved, Experimental Dihydroergocryptine The risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Dalfopristin. Experimental Dihydroergotamine The risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Dalfopristin. Approved, Investigational Ergonovine The risk or severity of adverse effects can be increased when Ergonovine is combined with Dalfopristin. Approved Ergotamine The risk or severity of adverse effects can be increased when Ergotamine is combined with Dalfopristin. Approved Fluvastatin The serum concentration of Fluvastatin can be increased when it is combined with Dalfopristin. Approved Ibrutinib The serum concentration of Ibrutinib can be increased when it is combined with Dalfopristin. Approved Lisuride The risk or severity of adverse effects can be increased when Lisuride is combined with Dalfopristin. Approved, Investigational Lovastatin The serum concentration of Lovastatin can be increased when it is combined with Dalfopristin. Approved, Investigational Lysergic Acid Diethylamide The risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Dalfopristin. Illicit, Investigational, Withdrawn Metergoline The risk or severity of adverse effects can be increased when Metergoline is combined with Dalfopristin. Experimental Methylergometrine The risk or severity of adverse effects can be increased when Methylergometrine is combined with Dalfopristin. Approved Methysergide The risk or severity of adverse effects can be increased when Methysergide is combined with Dalfopristin. Approved Mevastatin The serum concentration of Mevastatin can be increased when it is combined with Dalfopristin. Experimental Nicergoline The risk or severity of adverse effects can be increased when Nicergoline is combined with Dalfopristin. Approved, Investigational Pergolide The risk or severity of adverse effects can be increased when Pergolide is combined with Dalfopristin. Approved, Investigational, Vet Approved, Withdrawn Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Dalfopristin. Approved Pitavastatin The serum concentration of Pitavastatin can be increased when it is combined with Dalfopristin. Approved Pravastatin The serum concentration of Pravastatin can be increased when it is combined with Dalfopristin. Approved Rilpivirine The serum concentration of Rilpivirine can be increased when it is combined with Dalfopristin. Approved Rosuvastatin The serum concentration of Rosuvastatin can be increased when it is combined with Dalfopristin. Approved Simvastatin The serum concentration of Simvastatin can be increased when it is combined with Dalfopristin. Approved Terguride The risk or severity of adverse effects can be increased when Terguride is combined with Dalfopristin. Experimental Tolvaptan The serum concentration of Tolvaptan can be increased when it is combined with Dalfopristin. Approved - 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, 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) 11.38 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 72.94 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
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
- 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
- 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
- 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 June 02, 2018 09:49