What are the pharmacokinetics of nonnucleoside reverse transcriptase inhibitors (NNRTIs) in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

NNRTIs display considerable interindividual variability in their pharmacokinetic properties. All currently approved NNRTIs utilize the cytochrome P450 system for metabolism and exert varying induction and inhibition effects on specific isoenzymes (e.g., CYP3A4, CYP2C9). This results in a significant potential for drug-drug interactions (see Drug Interactions with Antiretroviral Therapy or DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents for additional information). [28, 35]

Delavirdine primarily uses the 3A4 isoenzyme for metabolism. Nevirapine is metabolized mainly by 3A4 with some secondary metabolism through 2B6. Efavirenz is primarily metabolized through 2B6 and secondarily through 3A4. Etravirine is a substrate of 3A4, 2C9, and 2C19. Rilpivirine is primarily metabolized by 3A4. [8]

With the exception of nevirapine, the NNRTIs are highly protein-bound (98-99%), primarily to albumin and alpha1 acid glycoprotein. The serum half-lives of the NNRTIs are fairly extended, ranging from 25-55 hours, except for delavirdine, which has a shorter half-life (2-11 h). [8, 28, 35]


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