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Pharmacokinetics of the active antifungal enantiomer, SCH 42427 (RR), and evaluation of its chiral inversion in animals following its oral administration and the oral administration of its racemate genaconazole (RR/SS)
- Source :
- Chirality. 14:436-441
- Publication Year :
- 2002
- Publisher :
- Wiley, 2002.
-
Abstract
- Genaconazole (SCH 39304) is a potent triazole antifungal agent that is active both orally and topically. Genaconazole is a racemic mixture which contains 50% of the RR (SCH 42427) and 50% of the SS (SCH 42426) enantiomers. The RR isomer accounts for most of the antifungal activity of genaconazole. Serum concentrations of the RR and SS enantiomers were analyzed by a chiral HPLC method which involved extraction of serum with organic solvent followed by separation on a Cyclobond I column and quantification by UV absorbance at 205 nm. The bioavailability and pharmacokinetic profiles of the two enantiomers after oral administration of the racemate (genaconazole) were very similar in cynomolgus monkeys. In rats following dosing with genaconazole, the RR enantiomer had a lower Cmax and a longer t1/2 than the SS enantiomer, while the AUC(I) values of the two enantiomers were similar. Based on chiral HPLC analysis, there was no evidence for the inversion of the RR to the SR isomer, or of the SS to the SR isomer, indicating that there was no chiral inversion of the RR or SS enantiomers in either species. Genaconazole at 20 mg/kg and the RR (SCH 42427) enantiomer at 10 mg/kg had very similar serum concentration–time profiles and Cmax, AUC(I), and t1/2 values for the RR enantiomer in both rats and monkeys, indicating that the two treatments were equivalent with respect to the bioavailability of the RR enantiomer. Chirality 14:436–441, 2002. © 2002 Wiley-Liss, Inc.
- Subjects :
- Male
Antifungal Agents
Cmax
Administration, Oral
Biological Availability
Pharmacology
Catalysis
Analytical Chemistry
Pharmacokinetics
Oral administration
Drug Discovery
polycyclic compounds
Animals
heterocyclic compounds
Chromatography, High Pressure Liquid
Spectroscopy
Chromatography
Chemistry
Organic Chemistry
Stereoisomerism
Triazoles
Rats
Bioavailability
Chiral column chromatography
Macaca fascicularis
Racemic mixture
Enantiomer
Chirality (chemistry)
Subjects
Details
- ISSN :
- 1520636X and 08990042
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Chirality
- Accession number :
- edsair.doi.dedup.....a7271f75d5bbe7e2c18cb9b3500bfc19