Steady‐State Pharmacokinetics of Etravirine and Lopinavir/Ritonavir Melt Extrusion Formulation, Alone and in Combination, in Healthy HIV‐Negative Volunteers. (24th January 2013)

• Record Type: Journal Article
• Authors: Schöller‐Gyüre, Monika; Kakuda, Thomas N.; Witek, James; Akuma, Sophie H.; Smedt, Goedele De; Spittaels, Kurt; Vyncke, Veerle; Hoetelmans, Richard M.W.
• Is Part Of: Journal of clinical pharmacology. Volume 53:Number 2(2013:Feb.)
• Page Start: 202
• Page End: 210
• Publication Date: 2013-01-24
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1177/0091270012445205
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcp445205-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="jcp445205-sec-0002" sec-type="section"> <title>Method</title> <p>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.</p> </sec> <sec id="jcp445205-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="jcp445205-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>