CYP3A5 interactions

CYP3A5 is the conditional half of CYP3A: most people of European ancestry express almost none of it, while many of African ancestry express a great deal.

Every CYP3A substrate is handled by both 3A4 and 3A5, so 3A5 rarely changes anything on its own. It matters when a drug has essentially no therapeutic margin and the extra enzyme meaningfully shifts clearance.

Tacrolimus is the case that reaches practice. An expresser clears it faster and needs a substantially higher starting dose to reach target trough; treated as a non-expresser, the patient is under-immunosuppressed at exactly the moment that matters most. Cyclosporine, sirolimus, everolimus, imatinib and vincristine are the other substrates shown here.

CYP3A5 genotype is one of the few pharmacogenetic results that changes a starting dose rather than merely explaining a level after the fact.