Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism

European Journal of Clinical Pharmacology
K ArakiK Otani

Abstract

To clarify the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of etizolam. The effects of itraconazole, a potent and specific inhibitor of CYP3A4, on the single oral dose pharmacokinetics and pharmacodynamics of etizolam were examined. Twelve healthy male volunteers received itraconazole (200 mg/day) or placebo for 7 days in a double-blind randomized crossover manner, and on the 6th day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function using the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured by means of high-performance liquid chromatography. Itraconazole treatment significantly increased the total area under the plasma concentration-time curve (AUC; 213+/-106 ng rectangle h/ml versus 326+/-166 ng rectangle h/ml, P<0.001) and the elimination half-life (12.0+/-5.4 h versus 17.3+/-7.4 h, P<0.01) of etizolam. The 90% confidence interval of the itraconazole/placebo ratio of the total AUC was 1.38-1.68, indicating a significant effect of itraconazole. No significant change was induced by itraconazole in the two pharmacodynamic parameters. The present study su...Continue Reading

Citations

Nov 2, 2005·European Journal of Clinical Pharmacology·T FukasawaK Otani
Mar 19, 2005·European Journal of Clinical Pharmacology·S KondoK Otani
Mar 8, 2007·European Journal of Clinical Pharmacology·Sutep Jaruratanasirikul, Somchai Sriwiriyajan
May 13, 2009·Journal of Neural Transmission·Arun K TiwariDaniel J Müller
May 29, 2012·International Journal of Clinical Oncology·Tetsuya SasakiYasutsuna Sasaki
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Nov 4, 2008·Forensic Science International : Synergy·Takuma NakamaeKatsuyoshi Kurihara
Jul 20, 2007·Journal of Clinical Pharmacy and Therapeutics·T FukasawaK Otani
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Sep 30, 2016·Forensic Science International : Synergy·Gudrun HøisethRitva Karinen
Feb 14, 2006·Rapid Communications in Mass Spectrometry : RCM·Hyojin KimKwang-Hyeon Liu
Jul 6, 2017·Journal of Clinical Pharmacology·Takehito YamamotoHiroshi Suzuki
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Apr 4, 2020·Drug and Alcohol Review·Suzanne Nielsen, Andrew McAuley
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Sep 1, 2006·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Toshiro NiwaAkira Takagi

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