Steady-State Pharmacokinetics of Etravirine and Lopinavir/Ritonavir Melt Extrusion Formulation, Alone and in Combination, in Healthy HIV-Negative Volunteers

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 int...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2013-02, Vol.53 (2), p.202-210
Main Authors: Schöller-Gyüre, Monika, Kakuda, Thomas N., Witek, James, Akuma, Sophie H., Smedt, Goedele De, Spittaels, Kurt, Vyncke, Veerle, Hoetelmans, Richard M.W.
Format: Article
Language:English
Subjects:
Adult
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - adverse effects
Anti-HIV Agents - pharmacokinetics
Cross-Over Studies
Drug Interactions
Drug Therapy, Combination
etravirine
Female
Gels
HIV
HIV Infections
Human immunodeficiency virus
Humans
lopinavir
Lopinavir - administration & dosage
Lopinavir - adverse effects
Lopinavir - pharmacokinetics
Male
Middle Aged
nonnucleoside reverse transcriptase inhibitor (NNRTI)
pharmacokinetics
Protease inhibitors
Pyridazines - administration & dosage
Pyridazines - adverse effects
Pyridazines - pharmacokinetics
Ritonavir - administration & dosage
Ritonavir - adverse effects
Ritonavir - pharmacokinetics
Young Adult
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Summary: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 (
ISSN:0091-2700
1552-4604
DOI:10.1177/0091270012445205