A comparison of the steady-state pharmacokinetics of nevirapine in men, nonpregnant women and women in late pregnancy.

Abstract

To evaluate the pharmacokinetics of nevirapine and any possible influencing factors in pregnant women (n = 16), nonpregnant women (n = 13) and men (n = 14), who received nevirapine 200 mg twice daily together with nucleoside reverse transcriptase inhibitors. Blood samples were taken for 12 h at steady state. Nevirapine concentrations were measured by liquid chromatography-tandem mass spectrometry. The influence of gender, age, body weight and comedication on minimum and maximum concentrations (C(min), C(max)), area under the concentration-time curve (AUC), total clearance (CL(tot)), half-life (t(1/2)) and volume of distribution (V(d)) was analysed by multivariate techniques. Mean [95% confidence interval (CI)]C(max), AUC(ss) and clearance were 5221 ng ml(-1) (4267, 6175), 50 789 ng (-1)h ml(-1) (43 453, 58 125) and 69.9 ml min(-1) for men, 5871 ng ml(-1) (4848, 6895), 57 045 ng h(-1) ml(-1) (45 997, 68 093) and 65.6 ml min(-1) for nonpregnant women and 4505 ng ml(-1) (3644, 5366), 44 579 ng h(-1) ml(-1) (36 564, 52 594) and 82.1 ml min(-1) for pregnant women. The differences between pregnant and nonpregnant women (% difference, 95% CI) in C(max) (-30.3; -28.5, -33.0), AUC(ss) (-28.0; - 25.8, - 29.5) and clearance (20.2; 26.6, 15.6) reached statistical significance (P = 0.010, P = 0.028 and P = 0.028, respectively). The multivariate analysis underscored the influence of bodyweight on the plasma exposure to nevirapine. Pregnant women exhibited an increased nevirapine clearance and comparably low plasma concentrations, whereas women with a low bodyweight achieved high plasma nevirapine concentrations. The large variability in nevirapine concentrations in women may lead to loss of efficacy and viral resistance, or drug toxicity, and therefore these patients should be monitored frequently.