Reduced etravirine levels after direct switch from efavirenz
30 December 2009. Related: PK and drug interactions.
Polly Clayden, HIV i-Base
Essential news from Liverpool University drug interaction resource (HIV-druginteractions.org). See also the comprehensive drug interaction and pharmacology reports from the 49th ICAAC earlier in this issue of HTB.
This study in 25 healthy volunteers assessed the pharmacokinetics of etravirine (400 mg once daily and 200 mg twice daily) without and with a preceding efavirenz intake period (600 mg once daily for 14 days). Etravirine pharmacokinetics were assessed before and after efavirenz intake.
Steady state etravirine pharmacokinetic parameters were significantly lower after efavirenz intake in the once daily and twice daily arms. Etravirine AUC, Cmax and Ctrough when given once daily decreased by 29%, 22% and 33%, respectively. When given twice daily, etravirine AUC, Cmax and Ctrough decreased by 28%, 21% and 37%, respectively. All subjects had detectable efavirenz concentrations 7 days after stopping efavirenz intake; 5/25 had concentrations above the suggested minimum effective concentration of 1000 ng/ml.
The authors conclude that the induction effect of efavirenz persists for at least 2 weeks after stopping drug intake, but that the decrease in etravirine is not likely to be clinically significant. However, further clinical data are warranted.
Ref: Boffito M, Jackson A, Lamorde M, et al. Pharmacokinetics and safety of etravirine administered once or twice daily after 2 weeks treatment with efavirenz in healthy volunteers. J Acquir Immune Defic Syndr, 2009, 52(2): 222-227.