2024-03-28T17:08:59Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:00021746
2022-04-27T10:00:59Z
2780:1499
2780:1504
2780:1505
2871:2876:1496
3:62:5592:1347
Effects of Mexiletine, a CYP1A2 Inhibitor, on Tizanidine Pharmacokinetics and Pharmacodynamics
本間, 真人
猪股, 伸一
田中, 誠
幸田, 幸直
Momo, Kenji
Homma, Masato
Osaka, Yoshiko
Inomata, Shin-ichi
Tanaka, Makoto
Kohda, Yukinao
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.
journal article
Sage Publications
2010-03
application/pdf
Journal of clinical pharmacology
3
50
331
337
http://hdl.handle.net/2241/108158
0091-2700
AA00695597
https://tsukuba.repo.nii.ac.jp/record/21746/files/JCP_50-3.pdf
eng
19789372
10.1177/0091270009341961
© American College of Clinical Pharmacology, Inc.