Trial reportBritish journal of clinical pharmacology2012
Effects of ketoconazole and valproic acid on the pharmacokinetics of the next generation NNRTI, lersivirine (UK-453,061), in healthy adult subjects.
Trial report in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 17 citations in OpenAlex.
- A semiphysiological population pharmacokinetic model for dynamic inhibition of liver and gut wall cytochrome P450 3A by voriconazole.Clinical pharmacokinetics · 2013Trial
- Independent predictors of delay in emergence from general anesthesia.Anesthesia progress · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the effect of inhibitors of cytochrome P450 (CYP) 3A4 and glucuronidation (UGT2B7) on the pharmacokinetics of lersivirine (UK-453,061), a next generation non-nucleoside reverse transcriptase inhibitor with a unique resistance profile, and to investigate the safety and tolerability of co-administration of lersivirine with these inhibitors.
methodsTwo open-label, randomized, placebo-controlled, crossover studies were conducted in healthy subjects. Study 1 investigated the effect of ketoconazole (400 mg once daily) on the pharmacokinetics of lersivirine (250 mg once daily). Subjects received ketoconazole 400 mg once daily or placebo on days 1-2 and received lersivirine 250 mg once daily and ketoconazole 400 mg once daily or placebo on days 3-9. Study 2 investigated the effect of valproic acid (VPA, sodium valproate, 1000 mg once daily) on the PK of lersivirine (500 mg once daily). On days 1-7, subjects received lersivirine 500 mg once daily plus either VPA 1000 mg or placebo.
resultsCompared with lersivirine alone, co-administration with ketoconazole increased the lersivirine mean area under the curve (AUC(0,24 h)) and maximum plasma concentration (C(max) ) by 82% (90% CI 74%, 91%) and 61% (90% CI 41%, 83%), respectively. VPA increased the mean lersivirine AUC(0,24 h) by 25% (90% CI 16%, 35%), with little effect on C(max) (2.5%, 90% CI -9%, 16%). There were no serious adverse events and no treatment-related discontinuations from either study.
conclusionsInhibition of CYP3A4 and UGT2B7 by ketoconazole increased lersivirine exposure. Inhibition of UGT2B7-mediated glucuronidation by VPA had a modest effect on lersivirine exposure. Co-administration of lersivirine with either ketoconazole or VPA appeared to be well tolerated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.