Pharmacokinetics of once daily darunavir/ritonavir and efavirenz

A two-way interaction exists between efavirenz and darunavir/ritonavir where coadministration decreased darunavir AUC (13%) and Ctrough (31%) and increased efavirenz AUC (21%) and Ctrough (17%). However these data were obtained with a lower than licensed twice-daily dose of darunavir/ritonavir and no data exist for once daily darunavir/ritonavir.

This study looked at the effect of efavirenz on the pharmacokinetics of once daily darunavir/ritonavir in healthy volunteers (n=12). Subjects received darunavir/ritonavir (900/100 mg once daily) for 10 days and then efavirenz (600 mg once daily) was added for 14 days. Darunavir-ritonavir was then stopped and efavirenz alone was given for 14 days. At the end of each period, samples were taken for pharmacokinetic analysis (AUC 0-24h)

Coadministration decreased darunavir Ctrough by 57% (from 2137±1034 to 1180±1138 ng/ml, mean±sd) and decreased AUC by 14%. Ritonavir Ctrough and AUC decreased by 54% and 26%, respectively, when given with efavirenz. The half-life of efavirenz was increased significantly in the presence of darunavir/ritonavir, but there was no change in efavirenz Ctrough and only a 9% decrease in AUC.

Although efavirenz reduced the trough concentrations of darunavir significantly, all trough concentrations remained above the EC50 for darunavir for the wild-type virus (55 ng/mL). However, there was considerable variability in trough darunavir concentration which, in a larger study, may result in some patients not achieving plasma concentrations 1.5 times that of the EC50 (a value that equates to an inhibitory quotient of more than 1.5 and predicted antiviral efficacy in previous studies). The clinical efficacy and durability of this regimen needs to be validated with a larger sample of treatment-naive patients.

Soon GH et al. Pharmacokinetics of darunavir at 900 milligrams and ritonavir at 100 milligrams once daily when coadministered with efavirenz at 600 milligrams once daily in healthy volunteers. Antimicrob Agents Chemother, 2010, 54(7): 2775-2780. http://www.ncbi.nlm.nih.gov/pubmed/20385850