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Pharmacokinetics and safety of etravirine administered once or twice daily after 2 weeks treatment with efavirenz in healthy volunteers.
- Source :
-
Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2009 Oct 01; Vol. 52 (2), pp. 222-7. - Publication Year :
- 2009
-
Abstract
- Objective: To assess the pharmacokinetics of etravirine once and twice daily without and with a preceding efavirenz intake period in healthy volunteers.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Alkynes
Anti-HIV Agents adverse effects
Benzoxazines adverse effects
Cyclopropanes
Drug Interactions
Female
Healthy Volunteers
Humans
Male
Middle Aged
Nitriles
Plasma chemistry
Pyridazines adverse effects
Pyrimidines
Young Adult
Anti-HIV Agents pharmacokinetics
Benzoxazines pharmacokinetics
Pyridazines pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1944-7884
- Volume :
- 52
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of acquired immune deficiency syndromes (1999)
- Publication Type :
- Academic Journal
- Accession number :
- 19620877
- Full Text :
- https://doi.org/10.1097/QAI.0b013e3181b061d0