BACKGROUND: A previous study investigating coadministration of etravirine, a nonnucleoside reverse transcriptase inhibitor, and lopinavir/ritonavir soft-gel formulation resulted in nonclinically relevant changes in etravirine and lopinavir exposure. The current study evaluated the pharmacokinetic interaction between etravirine and the lopinavir/ritonavir melt extrusion formulation. METHOD:Sixteen human immunodeficiency virus (HIV)-negative volunteers were randomized to either treatment sequence A/B or B/A, with 14 days- washout between treatments (treatment A: etravirine 200 mg bid for 8 days; treatment B: lopinavir/ritonavir 400/100 mg bid for 16 days with etravirine 200 mg bid on days 9-16). Steady-state pharmacokinetics were assessed for all antiretrovirals alone and coadministered; pharmacokinetic parameters were obtained by noncompartmental analysis. Safety and tolerability were assessed. RESULTS: Coadministration of etravirine and lopinavir/ritonavir resulted in a 35% decrease in etravirine exposure. Smaller decreases (<13%) were observed in lopinavir and ritonavir exposure. Six volunteers reported headache; 1 grade 3 triglyceride increase was reported. CONCLUSION:Lopinavir/ritonavir induced etravirine metabolism to a similar extent as most other boosted HIV protease inhibitors. The short-term coadministration of etravirine and lopinavir/ritonavir was well tolerated and did not lead to increased incidences of adverse events.
RCT Entities:
BACKGROUND: A previous study investigating coadministration of etravirine, a nonnucleoside reverse transcriptase inhibitor, and lopinavir/ritonavir soft-gel formulation resulted in nonclinically relevant changes in etravirine and lopinavir exposure. The current study evaluated the pharmacokinetic interaction between etravirine and the lopinavir/ritonavir melt extrusion formulation. METHOD: Sixteen human immunodeficiency virus (HIV)-negative volunteers were randomized to either treatment sequence A/B or B/A, with 14 days- washout between treatments (treatment A: etravirine 200 mg bid for 8 days; treatment B: lopinavir/ritonavir 400/100 mg bid for 16 days with etravirine 200 mg bid on days 9-16). Steady-state pharmacokinetics were assessed for all antiretrovirals alone and coadministered; pharmacokinetic parameters were obtained by noncompartmental analysis. Safety and tolerability were assessed. RESULTS: Coadministration of etravirine and lopinavir/ritonavir resulted in a 35% decrease in etravirine exposure. Smaller decreases (<13%) were observed in lopinavir and ritonavir exposure. Six volunteers reported headache; 1 grade 3 triglyceride increase was reported. CONCLUSION:Lopinavir/ritonavir induced etravirine metabolism to a similar extent as most other boosted HIV protease inhibitors. The short-term coadministration of etravirine and lopinavir/ritonavir was well tolerated and did not lead to increased incidences of adverse events.
Authors: Michelle A Kendall; Umesh Lalloo; Courtney V Fletcher; Xingye Wu; Anthony T Podany; Sandra W Cardoso; Prudence Ive; Constance A Benson Journal: Clin Infect Dis Date: 2021-08-16 Impact factor: 20.999
Authors: Nikki Mulligan; Stein Schalkwijk; Brookie M Best; Angela Colbers; Jiajia Wang; Edmund V Capparelli; José Moltó; Alice M Stek; Graham Taylor; Elizabeth Smith; Carmen Hidalgo Tenorio; Nahida Chakhtoura; Marjo van Kasteren; Courtney V Fletcher; Mark Mirochnick; David Burger Journal: Front Pharmacol Date: 2016-08-04 Impact factor: 5.810