In vitro and in vivo drug interactions involving human CYP3A

KE Thummel, GR Wilkinson - Annual review of pharmacology …, 1998 - annualreviews.org
KE Thummel, GR Wilkinson
Annual review of pharmacology and toxicology, 1998annualreviews.org
▪ Abstract Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many
chemically diverse drugs administered to humans. Moreover, its localization in high amounts
both in the small intestinal epithelium and liver makes it a major contributor to presystemic
elimination following oral drug administration. Drug interactions involving enzyme inhibition
or induction are common following the coadministration of two or more CYP3A substrates.
Studies using in vitro preparations are useful in identifying such potential interactions and …
Abstract
Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.
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