OBJECTIVE: To assess the pharmacokinetics of etravirine once and twice daily without and with a preceding efavirenz intake period in healthy volunteers. METHODS: Volunteers were randomized to receive etravirine 400 mg once daily (arm 1) or 200 mg twice daily (arm 2) for 14 days. All subjects underwent a washout period of 14 days and then took efavirenz 600 mg once daily for 14 days. Arm 1 and 2 restarted etravirine once and twice daily for 14 days. Etravirine pharmacokinetics was assessed for each phase (before and after efavirenz 14-day intake) on days 1 and 14. Efavirenz concentrations were measured daily for 14 days after intake withholding. Pharmacokinetic parameters were compared (before and after efavirenz 14-day intake) by determining geometric mean ratios and 90% confidence intervals. RESULTS:Twenty-five subjects (9 female) completed the study. Steady-state etravirine pharmacokinetic parameters were significantly lower after efavirenz intake in the once-daily and twice-daily arms: geometric mean ratios and 90% confidence intervals were 0.71 (0.62 to 0.81) for AUC 0-24, 0.78 (0.70 to 0.86) for Cmax, 0.67 (0.49 to 0.91) for Ctrough for once daily; and 0.72 (0.63 to 0.81) for AUC 0-12, 0.79 (0.70 to 0.90) for Cmax, and 0.63 (0.54 to 0.73) for Ctrough for twice daily. All subjects had detectable efavirenz concentrations 7 days after stopping efavirenz intake, 5 above the suggested minimum effective concentration of 1000 ng/mL. CONCLUSIONS: The induction effect of efavirenz persists for at least 2 weeks after stopping drug intake. The decrease in etravirine is not considered clinically significant. Further clinical data are warranted.
RCT Entities:
OBJECTIVE: To assess the pharmacokinetics of etravirine once and twice daily without and with a preceding efavirenz intake period in healthy volunteers. METHODS: Volunteers were randomized to receive etravirine 400 mg once daily (arm 1) or 200 mg twice daily (arm 2) for 14 days. All subjects underwent a washout period of 14 days and then took efavirenz 600 mg once daily for 14 days. Arm 1 and 2 restarted etravirine once and twice daily for 14 days. Etravirine pharmacokinetics was assessed for each phase (before and after efavirenz 14-day intake) on days 1 and 14. Efavirenz concentrations were measured daily for 14 days after intake withholding. Pharmacokinetic parameters were compared (before and after efavirenz 14-day intake) by determining geometric mean ratios and 90% confidence intervals. RESULTS: Twenty-five subjects (9 female) completed the study. Steady-state etravirine pharmacokinetic parameters were significantly lower after efavirenz intake in the once-daily and twice-daily arms: geometric mean ratios and 90% confidence intervals were 0.71 (0.62 to 0.81) for AUC 0-24, 0.78 (0.70 to 0.86) for Cmax, 0.67 (0.49 to 0.91) for Ctrough for once daily; and 0.72 (0.63 to 0.81) for AUC 0-12, 0.79 (0.70 to 0.90) for Cmax, and 0.63 (0.54 to 0.73) for Ctrough for twice daily. All subjects had detectable efavirenz concentrations 7 days after stopping efavirenz intake, 5 above the suggested minimum effective concentration of 1000 ng/mL. CONCLUSIONS: The induction effect of efavirenz persists for at least 2 weeks after stopping drug intake. The decrease in etravirine is not considered clinically significant. Further clinical data are warranted.
Authors: V Michaud; E Ogburn; N Thong; A O Aregbe; T C Quigg; D A Flockhart; Z Desta Journal: Clin Pharmacol Ther Date: 2012-02-08 Impact factor: 6.875
Authors: Luis F López-Cortés; Pompeyo Viciana; José A Girón-González; Alberto Romero-Palacios; Manuel Márquez-Solero; Maria A Martinez-Perez; Miguel A López-Ruz; Javier de la Torre-Lima; Francisco Téllez-Pérez; Marcial Delgado-Fernández; Milagros Garcia-Lázaro; Fernando Lozano; Mohamed O Mohamed-Balghata Journal: PLoS One Date: 2014-05-16 Impact factor: 3.240