Leitz G, Lamson M, Lionetti D, Sabo J, Myers M; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 55 (abstract no. 12217).
Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, USA.
OBJECTIVE: Nevirapine (NVP) is a non nucleoside RT inhibitor of HIV that is metabolized by Cytochrome P450 3A in the liver. Lamivudine (3TC) is a nucleoside RT inhibitor which is largely excreted unchanged in the urine. The two drugs are frequently used in combination with other annti-Retrovirals. This study was designed to determine the effects of multiple-dose NVP administration on the steady-state serum concentrations of 3TC and the effect of 3TC on NVP pharmacokinetics when administered together on a background of anti-Retroviral therapy. METHODS: A population pharmacokinetic approach was employed to assess the effects of nevirapine on the pharmacokinetics of lamivudine in 100 patients who were randomized into a large clinical endpoint study. Patients received either NVP (200 mg q.d. for two weeks then 200 mg b.i.d.) + 3TC (150 mg b.i.d.) or placebo + 3TC on an anti-Retroviral background therapy. At the beginning of the study patients were instructed to take their morning NVP/3TC doses together at the same time every day and to take their evening doses 12 hours later. Four weeks after treatment start, blood samples to determine NVP/3TC concentrations were taken at defined time points. In addition, patients were required to document the time they took the morning dose of NVP/3TC that day. RESULTS: The preliminary results suggest that nevirapine co-administration resulted in a non-significant increase in lamivudine serum concentrations from 792 +/- 612 ng/mL (725 ng/mL, median) to 917 +/- 719 (759 ng/mL, median). The effects (apparent clearance, volume of distribution, T1/2) of nevirapine on lamivudine as well as those of lamivudine on nevirapine will be presented utilizing the mixed-effects population pharmacokinetic program NONMEM.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Biomedical Research
- Drug Interactions
- HIV Infections
- HIV Seropositivity
- Humans
- Lamivudine
- Nevirapine
Other ID:
UI: 102227245
From Meeting Abstracts