IngentaConnect In vivo inhibition of CYP2C19 but not CYP2D6 by fluvoxamine

Authors: XU, ZHEN-HUA¹; XIE, HONG-GUANG¹; ZHOU, HONG-HAO¹

Source: British Journal of Clinical Pharmacology, Volume 42, Number 4, October 1996 , pp. 518-521(4)

Abstract:

Studies were performed in eight healthy extensive metabolizers of mephenytoin and debrisoquine to determine the effect of fluvoxamine on the activities of S-mephenytoin 4′-hydroxylase (CYP2C19) and metoprolol α-hydroxylase (CYP2D6). Therapeutic dosing with fluvoxamine (100 mg day⁻¹) for 2 weeks caused a significant increase in the 0-8 h urinary S/R ratio of mephenytoin from 0.16 to 0.55 (95% confidence interval for difference between means: 0.28-0.50; P<0.01), accompanied by a 54% reduction in the 0-8 h urinary recovery of 4′-hydroxymephenytoin (95% confidence interval for difference between means: 3.64-16.24 mg; P<0.05). However, this did not alter the assigned phenotype of any of the subjects based on the established antimode of 0.95 (S/R-mephenytoin ratio). Two weeks after fluvoxamine was discontinued, both metabolic indices returned to their pre-study values. By contrast, fluvoxamine had no effect on either 0-8 h urinary metoprolol/α-hydroxymetoprolol ratio (95% confidence interval for difference between means: −0.38-0.46; P >0.05) or the 0-8 h urinary recovery of α-hydroxymetoprolol (95% confidence interval for difference between means: −0.61-0.70 mg; P >0.05). These results indicated fluvoxamine has a modest inhibitory effect on the activity of CYP2C19, but no effect on that of CYP2D6 in vivo.

Keywords: fluvoxamine; mephenytoin; metoprolol; CYP2D6; CYP2C19 inhibition

Document Type: Research article

DOI: 10.1046/j.1365-2125.1996.45319.x

Affiliations: 1: Pharmacogenetics Research Institute, Hunan Medical University, Changsha, Hunan 410078, China

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