IN-VITRO AND IN-VIVO DRUG-INTERACTIONS INVOLVING HUMAN CYP3A

Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its l ocalization in high amounts both in the small intestinal epithelium an d liver makes it a major contributor to presystemic elimination follow ing oral drug administration. Drug interactions involving enzyme inhib ition 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 ex trapolation 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 clin ical experience. In many instances, the extent of such drug interactio ns is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.