Antiviral Effect and Pharmacokinetic Interaction between Nevirapine and Indinavir in Persons Infected with Human Immunodeficiency Virus Type 1

Abstract

Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were </=20 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with nevirapine.

Indinavir Trough Concentration as a Determinant of Early Nephrolithiasis in HIV-1-Infected Adults

“…Contrary to the present study, no specific approach was used to validate this cut-off. Even if the cut-off value of 1000 ng/mL, reported in our study, seems high compared with the range of 150 ng/mL to 500 ng/mL reported by others (6,7,23,33), it may be explained by the modelling estimate of C res , precisely 8 hours after last intake.…”

“…therapeutic drug monitoring (TDM), has shown a large interest in many diseases (3)(4)(5), to improve efficacy and minimize toxicity. Moreover, PIs are good candidates for TDM because of high inter-patient variability in plasma concentrations, binding to plasma proteins, P450 3A4 cytochrom metabolism, short half-life, drug-food and drug-drug interactions (6,7) that may lead to inadequate PIs exposure among patients receiving the same dose.…”

Drug Interactions Between Antiretroviral Drugs and Comedicated Agents

“…Therapeutic drug monitoring (TDM) of PIs and NNRTIs is currently valued as an additional clinical tool in HIV care, since relationships have been described between plasma concentrations and efficacy and/or toxicity. [4,[8][9][10][11] When TDM of drugs is suggested, the plasma concentration needs to be quantified with a validated method and interpretation of the result should be performed by a qualified person (e.g. clinical pharmacologist).…”

“…Awareness, recognition and management of drug interactions are important in the optimisation of pharmaceutical care to HIVinfected patients, helping to prevent adverse events and/or loss in efficacy of the drugs administered. [8][9][10][11] This review presents a tabulated overview of interactions of antiretroviral drugs and comedicated agents based on drug-drug interaction studies, case reports, population pharmacokinetic data, in vitro studies and theoretical grounds. Furthermore, a concise review is presented of the pharmacokinetics and mechanisms of interaction of antiretroviral drugs.…”

Selecting patients who can be re-challenged with Nevirapine in case of skin rash with Efavirenz – A Study

“…5,6 In comparison, NVP, a dipyridodiazepinone and EFV, a benzoxazinone, have shown better tolerability and antiretroviral efficacy. 7,8 Skin rash is the key adverse effect observed with NVP and EFV. 9,10 Their individual propensities to cause side effects differ, with NVP showing a higher risk of cutaneous and hepatic reactions, and EFV, in addition to skin rash, having a higher risk of central nervous system effects.…”