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- W2891432462 abstract "A sensitive, ultraviolet, spectrophotometric, high-performance liquid chromatographic method (using dinitrophenyl derivatives of drug and metabolites) for the simultaneous determination of perhexiline and its major metabolites in biological fluids was developed and validated. The procedure was employed successfully in pharmacokinetic studies of perhexiline in healthy, adult volunteers. Following oral administration of perhexiline to human volunteers, considerable inter-individual variation in the rates of drug absorption occurs. Extensive pre-systemic metabolism was observed following drug ingestion, with considerable individual variation in the AUC of plasma perhexiline. Significantly more unchanged perhexiline was available in the systemic circulation following the administration of (+) perhexiline than after either its optical antipode or the racemate; of the three dosage forms the (-) enantiomer was associated with the lowest plasma perhexiline levels. Perhexiline is metabolized by the cytochrome P-450 dependent mixed function oxidase system in the liver. In humans, cis-hydroxylation is generally the predominant metabolic pathway for racemic perhexiline with trans-hydroxylation probably playing a major role in individuals with impaired drug oxidative capacity. Cis-hydroxylation of perhexiline in humans may exhibit saturable kinetics. The metabolism of perhexiline exhibits complex stereoselectivity. In man, cis- and trans-hydroxylation are the preferred routes of metabolism following ingestion of (-) and (+) perhexiline respectively. The (-) enantiomer is metabolized at a faster rate than its optical antipode either in in vivo in humans, or in vitro in man and the rat. Drug accumulation and hence drug induced-toxicity, on prolonged Pexid therapy in angina patients is more likely to occur with the (+) than with either the (-)enantiomer or racemate and least with the (-) enantiomer. Defective function of the liver monooxygenase system possibly due to defective cytochrome P-450-substrate interaction and/or abnormal microenviroment of cytochrome P-450 may be the molecular mechanism of impaired hydroxylation of perhexiline." @default.
- W2891432462 created "2018-09-27" @default.
- W2891432462 creator A5012557833 @default.
- W2891432462 date "1983-01-01" @default.
- W2891432462 modified "2023-09-23" @default.
- W2891432462 title "Clinical pharmacokinetics of perhexiline." @default.
- W2891432462 hasPublicationYear "1983" @default.
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