Abstract
While it is difficult to secure the abundant systemic exposure of CYP3A/P-gp substrate drugs such as HIV protease inhibitors, pharmacokinetic booster contributes to the drastic improvement of their systemic exposure by potent inhibition of their metabolic and efflux pathways. Traditionally, low dose of ritonavir (compared with therapeutic dose for HIV treatment) has been used. Recently, cobicistat, a structurally-related compound of ritonavir without any pharmacological effect and induction potency of metabolic enzymes, has been created as a pure booster and is clinically used with other drugs as a combination drug. Both ritonavir and cobicistat potently inhibit intestinal and hepatic CYP3A, whereas only ritonavir also leads to the induction of multiple metabolic enzymes. Thus, in the case of the change of prescription between ritonavir and cobicistat, we must pay attention to the significant alteration in the pharmacokinetics of co-administered drugs.
