Lack of indinavir effects on methadone disposition despite inhibition of hepatic and intestinal cytochrome P4503A (CYP3A).

Background: Methadone disposition and pharmacodynamics are highly susceptible to interactions with antiretroviral drugs. Methadone clearance and drug interactions have been attributed to cytochrome P4503A4 (CYP3A4), but actual mechanisms are unknown. Drug interactions can be clinically and mechanistically informative.

Methadone metabolism and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A) activity.

Background: Methadone plasma concentrations are decreased by nelfinavir. Methadone clearance and the drug interactions have been attributed to CYP3A4, but actual mechanisms of methadone clearance and the nelfinavir interaction are unknown. We assessed nelfinavir effects on methadone pharmacokinetics and pharmacodynamics, intestinal and hepatic CYP3A4/5 activity, and intestinal P-glycoprotein transport activity.

Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal drug transport: insights from methadone interactions with ritonavir/indinavir.

Background: Methadone clearance is highly variable, and drug interactions are problematic. Both have been attributed to CYP3A, but actual mechanisms are unknown. Drug interactions can provide such mechanistic information.