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Journal of clinical pharmacology >
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http://hdl.handle.net/2241/108158
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| Title: | Effects of Mexiletine, a CYP1A2 Inhibitor, on Tizanidine Pharmacokinetics and Pharmacodynamics |
| Authors: | Momo, Kenji
Homma, Masato
Osaka, Yoshiko
Inomata, Shin-ichi
Tanaka, Makoto
Kohda, Yukinao
本間, 真人
猪股, 伸一
田中, 誠
幸田, 幸直 |
| Issue Date: | Mar-2010 |
| Publisher: | Sage Publications |
| Journal Title: | Journal of clinical pharmacology |
| Volume: | 50 |
| Issue: | 3 |
| Start Page: | 331 |
| End Page: | 337 |
| DOI: | 10.1177/0091270009341961 |
| PMID: | 19789372 |
| 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·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. |
| URI: | http://hdl.handle.net/2241/108158 |
| Rights: | © American College of Clinical Pharmacology, Inc. |
| Text Version: | author |
| Appears in Collections: | 幸田 幸直 (Kohda Yukinao)
田中 誠 (TANAKA MAKOTO)
猪股 伸一 (Inomata Shinichi)
本間 真人 (Homma Masato)
Journal of clinical pharmacology
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