1. Effects of mexiletine, a CYP1A2 inhibitor, on tizanidine pharmacokinetics and pharmacodynamics.
- Author
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Momo K, Homma M, Osaka Y, Inomata S, Tanaka M, and Kohda Y
- Subjects
- Adult, Antihypertensive Agents administration & dosage, Antihypertensive Agents adverse effects, Antihypertensive Agents blood, Area Under Curve, Blood Pressure drug effects, Chromatography, High Pressure Liquid, Clonidine administration & dosage, Clonidine adverse effects, Clonidine blood, Clonidine pharmacokinetics, Dose-Response Relationship, Drug, Drug Administration Schedule, Half-Life, Humans, Male, Sleep Stages drug effects, Tandem Mass Spectrometry, Xerostomia chemically induced, Xerostomia drug therapy, Anti-Arrhythmia Agents pharmacology, Antihypertensive Agents pharmacokinetics, Clonidine analogs & derivatives, Cytochrome P-450 CYP1A2 Inhibitors, Drug Interactions, Mexiletine pharmacology
- Abstract
The aim of this study was to determine whether mexiletine, a CYP1A2 inhibitor, altered the pharmacokinetics and pharmacodynamics of tizanidine. The pharmacokinetics of tizanidine were examined in an open-label study in 12 healthy participants after a single dose of tizanidine (2 mg) with and without mexiletine coadministration (50 mg, 3 times as a pretreatment for a day and 2 times on the study day). Compared with tizanidine alone, mexiletine coadministration increased the peak plasma concentration (1.8 +/- 0.8 vs 5.3 +/- 1.8 ng/mL), area under the curve (4.5 +/- 2.2 vs 15.4 +/- 6.5 ng x h/mL), and the half-life (1.3 +/- 0.2 vs 1.8 +/- 0.7 h) of tizanidine, respectively (P < .05). Reduction in systolic blood pressure (-10 +/- 8 vs -24 +/- 7 mm Hg) and diastolic blood pressure (-10 +/- 7 vs -18 +/- 8 mm Hg) after tizanidine administration was also significantly enhanced by coadministration of mexiletine (P < .01). Of the 15 patients treated with tizanidine and mexiletine, 4 suffered tizanidine-induced adverse effects such as drowsiness and dry mouth in the retrospective survey. Present results suggested that coadministration of mexiletine increased blood tizanidine concentrations and enhanced tizanidine pharmacodynamics in terms of reduction in blood pressure and adverse symptoms.
- Published
- 2010
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