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Steady‐State Pharmacokinetics of Etravirine and Lopinavir/Ritonavir Melt Extrusion Formulation, Alone and in Combination, in Healthy HIV‐Negative Volunteers
Author(s) -
SchöllerGyüre Monika,
Kakuda Thomas N.,
Witek James,
Akuma Sophie H.,
Smedt Goedele De,
Spittaels Kurt,
Vyncke Veerle,
Hoetelmans Richard M.W.
Publication year - 2013
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270012445205
Subject(s) - etravirine , ritonavir , lopinavir , pharmacokinetics , lopinavir/ritonavir , pharmacology , medicine , human immunodeficiency virus (hiv) , virology , antiretroviral therapy , viral load
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.