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Clinical Pharmacokinetics of Non-Nucleoside Reverse Transcriptase Inhibitors

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Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a diverse group of compounds that induce allosteric changes in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, thus rendering the enzyme incapable of converting viral RNA to DNA. Unlike nucleoside analogue inhibitors of reverse transcriptase, NNRTIs do not require sequential phosphorylation to elicit antiretroviral activity.

There are currently 3 approved NNRTIs: nevirapine, delavirdine and efavirenz. Although possessing a common mechanism of action, these agents can be differentiated by both molecular and pharmacokinetic characteristics. Each of the NNRTIs is metabolised to some degree by the cytochrome P450 (CYP) system of enzymes, making them prone to clinically significant drug interactions. In addition, they elicit variable effects on other medications, acting as either inducers or inhibitors of drugs metabolised by CYP. These drug interactions are an important consideration in the clinical use of these agents as a part of combination antiretroviral therapy. Additional factors such as the influence of food and pH on oral absorption, and protein binding, must also be considered.

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Acknowledgements

This study was supported in part by the Adult AIDS Clinical Trials Group.

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Authors and Affiliations

  1. Laboratory for Antiviral Research, University at Buffalo, The State University of New York School of Pharmacy and Pharmaceutical Sciences, 311 Hochstetter Hall, Amherst, 14260, USA

    Patrick F. Smith, Robert DiCenzo & Gene D. Morse

  2. Departments of Medicine and Pharmacy, Roswell Park Cancer Institute, Buffalo, New York, USA

    Patrick F. Smith

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  1. Patrick F. Smith
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Correspondence to Patrick F. Smith.

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Smith, P.F., DiCenzo, R. & Morse, G.D. Clinical Pharmacokinetics of Non-Nucleoside Reverse Transcriptase Inhibitors. Clin Pharmacokinet 40, 893–905 (2001). https://doi.org/10.2165/00003088-200140120-00002

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