Single dose pharmacokinetics and bioavailability of nevirapine in healthy volunteers

Abstract

The results of two randomized, single‐dose, crossover bioavailability studies are presented which describe the pharmacokinetics and oral bioavailability of nevirapine, a novel nonnucleoside antiretroviral drug. In the first study 12 healthy male volunteers received nevirapine 15 mg via short‐term i.v. infusion or orally as a 50 mg tablet or reference solution (50 mg/200 mL). Following the i.v. dose, nevirapine had a low systemic clearance (Mean±S.D., Cl=1.4±0.3 L/h) and a prolonged elimination phase (t1/2β=52.8±14.8 h; MRT=81.4±22.4 h). Nevirapine absolute bioavailability was 93±9% and 91±8% for the tablet and oral solution, respectively. In the second study, 24 healthy male volunteers were administered nevirapine as a 200 mg production‐line tablet or oral reference solution (200 mg/200 mL). There was no significant difference in bioavailability between the tablet and reference solution. Overall, comparison of the pharmacokinetic parameters between the 50 and 200 mg doses indicates that nevirapine is well absorbed at clinically relevant doses. The absorption profiles using deconvolution revealed no evidence of differential enzyme induction between the two doses or routes of administration following a single dose. Copyright © 1999 John Wiley & Sons, Ltd.

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

“…Enterohepatic recycling of nevirapine has been shown in rats [37] and is suggested to be present in humans due to the presence of a second peak concentration following the administration of oral and intravenous single doses [32,38,39]. In this study, a second peak concentration was seen in some patients, but not in others who may have eaten at times different from the sampling times.…”

Pharmacokinetics of nevirapine and lamivudine in patients with HIV-1 infection

“…The pharmacokinetics of nevirapine were consistent with that of several earlier trials 5,6,8,19 . Therefore, the 2 drugs can be administered concurrently to HIV-1 -infected patients without regard to dosage adjustment for either drug.…”

Solvated Crystalline Forms of Nevirapine: Thermoanalytical and Spectroscopic Studies

“…It is a well-known antiretroviral agent belonging to nonnucleoside reverse transcriptase inhibitor and is used in the treatment of AIDS. The drug belongs to class II of the Biopharmaceutics Classification System with a pK a of 2.8 and is practically insoluble in water (solubility ∼0.1 mg/ml), and consequently, dissolution of the drug has been considered to be the rate-limiting step for absorption (21)(22)(23)(24). The amide function (-CONH) in the drug makes it a potential candidate for crystal polymorphism or pseudopolymorphism upon interaction with various solvents, thereby displaying unique physicochemical properties (25).…”