Answer
Pharmacokinetic (PK) enhancing is used to increase exposure of an ARV by concomitantly administering a drug that inhibits the enzymes that metabolize the ARV. Two agents are available in the United States for use as PK enhancers (ritonavir, cobicistat [COBI]). Both of these drugs are potent CYP3A4 inhibitors, resulting in higher drug exposures ARVs are metabolized by this pathway. Importantly, RTV and COBI may have different effects on other CYP or UGT metabolizing enzymes and drug transporters. Complex or unknown mechanisms of PK-based interactions preclude extrapolation of RTV drug interactions to certain COBI interactions, such as interactions with warfarin, phenytoin, voriconazole, oral contraceptives, certain HMG-CoA reductase inhibitors (or statins), and other drugs. [2]
For more information, see the NIH Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.
Table 3. Pharmacokinetic Enhancers and Their Metabolic Pathways [2] (Open Table in a new window)
Generic (Brand) |
Metabolized by (ie, Substrate of) |
Induces |
Inhibits |
Cobicistat (Tybost) COBI |
CYP3A4 |
- |
CYP3A4 CYP2D6 P-gp |
Ritonavir (Norvir) RTV |
CYP3A4 CYP2D6 P-gp |
CYP1A2 CYP2C8 CYP2C9 CYP2C19 UGT1A1 |
CYP3A4 (primarily) CYP2D6 (less extent) P-gp |