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Effects of Mexiletine, a CYP1A2 Inhibitor, on Tizanidine Pharmacokinetics and Pharmacodynamics
Author(s) -
Momo Kenji,
Homma Masato,
Osaka Yoshiko,
Inomata Shinichi,
Tanaka Makoto,
Kohda Yukinao
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009341961
Subject(s) - tizanidine , mexiletine , pharmacokinetics , pharmacodynamics , medicine , pharmacology , anesthesia , spasticity
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·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.