The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

Objective: To investigate and to compare the steady-state plasma pharmacoki netics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. Design: Open-label, randomized, cross-over study. Methods: Twenty HIV-1-infected individuals who already used nevirapine as p art of their antiretroviral regimen were randomized to continue their curre nt regimen (200 mg twice daily) or to switch to the alternate regimen (400 mg once daily). The steady-state plasma pharmacokinetics of nevirapine were assessed after 2 weeks during a 24-h period. Subsequently, patients were s witched to the alternate regimen and the pharmacokinetics of nevirapine wer e assessed again after 2 weeks. Noncompartmental methods were used to calcu late the area under the plasma concentration versus time curve (AUC([24h])) , and the maximal (C-max) and minimal plasma concentration (C-min), the tim e to C-max (t(max)), the plasma elimination half-life (t(1/2)), the apparen t oral clearance (Cl/F) and the apparent volume of distribution (V/F). Diff erences in these pharmacokinetic parameters for the two dosing regimens wer e tested using ANOVA. Results: The exposure to nevirapine, as measured by the AUC([24h]), was not significantly different between the 400 mg once daily and 200 mg twice dai ly dosing regimen (P = 0.60). Furthermore, the values for t(max) t(1/2) Cl/ F and V/F were not significantly different between the two dosing regimens (P greater than or equal to 0.08). However, C-max and C-min were higher and lower, respectively, when nevirapine was used in the once daily regimen as compared with the twice daily regimen. The median values for C-max and C-m in as measured for the once daily and twice daily regimens were 6.69 and 5. 74 mu g/ml, respectively(P = 0.03), and 2.88 and 3.73 mu g/ml, respectively (P < 0.01). Conclusion: These data show that the daily exposure to nevirapine, as measu red by the plasma AUC([24h]), is not different between a 400 mg once daily and a 200 mg twice daily dosing regimen. However, C-max and C-min are highe r and lower, respectively, for the once daily regimen as compared with the twice daily regimen. The clinical implications of these differences remain to be established. (C) 2000 Lippincott Williams & Wilkins.