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- W2023441790 abstract "Background Chlormethiazole has been shown in in vitro studies, with use of rat and human liver microsomes, to specifically inhibit cytochrome P4502E1 (CYP2E1)—mediated activity by inhibition of the rate of CYP2E1 gene transcription. It is known that CYP2E1 is involved in the activation of many low-molecular-weight toxins and carcinogens and may be involved in the development of alcohol-induced liver disease. Methods The pharmacokinetics of a single oral dose of 250 mg chlorzoxazone, a marker of the activity of CYP2E1, were measured in five healthy drug-free volunteers and in 16 patients with alcoholism receiving 1.2 gm or 2.4 gm chlormethiazole per day for 1, 2, or 3 days. The patients were starting an alcohol-withdrawal program and were supposed to have an induced CYP2E1 activity. Results The results suggest that chlormethiazole strongly decreased chlorzoxazone clearance in the patients with alcoholism compared with clearance in the control subjects (3.98 ± 1.8 L/hr versus 12.7 ± 5.6 L/hr; p < 0.005), prolonged the elimination half-life (3.91 ± 1.23 hours versus 1.12 ± 0.34 hours; p < 0.001), and caused a threefold increase in the area under the concentration versus time curve of chlorzoxazone (73.0 ± 35.5 mg · hr/L versus 21.3 ± 13.7 mg · hr/L; p < 0.005). They also suggest that chlormethiazole significantly decreased the area under the concentration versus time curve of the metabolite 6-hydroxychlorzoxazone (4.56 ± 1.27 mg · hr/L versus 7.1 ± 1.84 mg · hr/L; p < 0.05). Conclusion Chlormethiazole administration seems to result in a marked reduction of CYP2E1 activity in subjects with high CYP2E1 activity and could at least partially explain the claimed hepatoprotective action of this drug. Clinical Pharmacology & Therapeutics (1998) 64, 52–57; doi:" @default.
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- W2023441790 title "Inhibition of CYP2E1 by chlormethiazole as measured by chlorzoxazone pharmacokinetics in patients with alcoholism and in healthy volunteers" @default.
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