What are drug interactions with pharmacokinetic (PK) enhancers (boosting agents) in antiretroviral therapy?

Updated: Jul 12, 2021
  • Author: Shahab Qureshi, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

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


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