Bioinversion ofR-flurbiprofen toS-flurbiprofen at various dose levels in rat, mouse, and monkey
| Autor: | Darko Kantoci, William J. Wechter, Douglas D. Leipold, E. David Murray, David D. Quiggle |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Drug Time Factors media_common.quotation_subject Pharmacology Catalysis Analytical Chemistry Rats Sprague-Dawley Guinea pig Mice Sex Factors Species Specificity Pharmacokinetics Drug Discovery Animals Humans Chromatography High Pressure Liquid Spectroscopy media_common Dose-Response Relationship Drug biology Chemistry Anti-Inflammatory Agents Non-Steroidal Organic Chemistry Stereoisomerism Haplorhini Metabolism R-flurbiprofen biology.organism_classification S-flurbiprofen Rats Mice Inbred C57BL Dose–response relationship Flurbiprofen Models Chemical Area Under Curve Female Propionates |
| Zdroj: | Chirality. 16:379-387 |
| ISSN: | 1520-636X 0899-0042 |
| DOI: | 10.1002/chir.20053 |
| Popis: | Information about the potential and extent of bioinversion of chiral drugs in laboratory animal species and humans is critical to the interpretation of preclinical pharm-tox studies with these drugs. Unlike in the dog, guinea pig, and rabbit, in humans the 2-arylpropionic acid (APA) R-flurbiprofen (R-FB) undergoes very little bioinversion to S-flurbiprofen. The primary objective of this research was to identify laboratory animal species with an R- to S-bioinversion profile similar to humans. Detailed evaluations of the pharmacokinetics parameters of R-flurbiprofen in male and female rats and mice, and male nude rats and monkeys demonstrated R- to S-bioinversion of 30% (average) in monkeys, 15-24% in mice, and approximately 4% in rats. To date, no laboratory animal species has been identified with an R-flurbiprofen bioinversion profile identical to humans. However, the rat has a bioinversion profile sufficiently similar to humans to be useful for preclinical. |
| Databáze: | OpenAIRE |
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