Once-daily nevirapine dosing: a pharmacokinetics, efficacy and safety review.
In the context of attempts to simplify treatment regimens and enhance adherence, there is great interest in once-daily dosing regimens for the treatment of HIV-1 infection. Nevirapine has a long half-life and achieves high steady-state plasma concentrations relative to the concentration required to inhibit 50% viral replication in vitro (IC(50)) in patients. For this reason, it has been considered as a once-daily antiretroviral. Pharmacokinetic and efficacy data support the use of this dosing approach, but excess rash and lingering concerns over liver toxicity preclude use of once-daily dosed nevirapine at this time. Tolerance to high nevirapine concentrations may develop when dose escalation is used during initiation of therapy. It is theoretically possible that the benefits of once-daily dosing may be achieved without excess toxicity by switching to once-daily nevirapine following several months of twice-daily administration. This dosing strategy is currently under evaluation.
Cooper
C L
CL
University of Ottawa, Ottawa Hospital Division of Infectious Diseases, and Health Research Institute, Ottawa, Ontario, Canada. ccooper@ottawahospital.on.ca
van Heeswijk
R P G
RP
D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D004361:Drug Tolerance; D005076:Exanthema / Q000139:chemically induced; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019829:Nevirapine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine