Steady-state pharmacokinetics of etravirine and lopinavir/ritonavir melt extrusion formulation, alone and in combination, in healthy HIV-negative volunteers
© The Author(s) 2012..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Journal of clinical pharmacology - 53(2013), 2 vom: 11. Feb., Seite 202-10 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schöller-Gyüre, Monika [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.07.2013 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/0091270012445205 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM225281805 |
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| 024 | 7 | |a 10.1177/0091270012445205 |2 doi | |
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| 035 | |a (NLM)23436265 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Schöller-Gyüre, Monika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Steady-state pharmacokinetics of etravirine and lopinavir/ritonavir melt extrusion formulation, alone and in combination, in healthy HIV-negative volunteers |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.07.2013 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2012. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Gels |2 NLM | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 650 | 7 | |a Pyridazines |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a etravirine |2 NLM | |
| 650 | 7 | |a 0C50HW4FO1 |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Kakuda, Thomas N |e verfasserin |4 aut | |
| 700 | 1 | |a Witek, James |e verfasserin |4 aut | |
| 700 | 1 | |a Akuma, Sophie H |e verfasserin |4 aut | |
| 700 | 1 | |a De Smedt, Goedele |e verfasserin |4 aut | |
| 700 | 1 | |a Spittaels, Kurt |e verfasserin |4 aut | |
| 700 | 1 | |a Vyncke, Veerle |e verfasserin |4 aut | |
| 700 | 1 | |a Hoetelmans, Richard M W |e verfasserin |4 aut | |
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