In vivo inhibition of CYP2C19 but not CYP2D6 by fluvoxamine

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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; P0.05) 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.

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