Document Detail

Effects of mexiletine, a CYP1A2 inhibitor, on tizanidine pharmacokinetics and pharmacodynamics.
MedLine Citation:
PMID:  19789372     Owner:  NLM     Status:  MEDLINE    
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.
Kenji Momo; Masato Homma; Yoshiko Osaka; Shin-ichi Inomata; Makoto Tanaka; Yukinao Kohda
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article     Date:  2009-09-29
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  50     ISSN:  1552-4604     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-19     Completed Date:  2010-05-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  331-7     Citation Subset:  IM    
Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anti-Arrhythmia Agents / pharmacology*
Antihypertensive Agents / administration & dosage,  adverse effects,  blood,  pharmacokinetics*
Area Under Curve
Blood Pressure / drug effects
Chromatography, High Pressure Liquid
Clonidine / administration & dosage,  adverse effects,  analogs & derivatives*,  blood,  pharmacokinetics
Cytochrome P-450 CYP1A2 / antagonists & inhibitors*
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Interactions*
Mexiletine / pharmacology*
Sleep Stages / drug effects
Tandem Mass Spectrometry
Xerostomia / chemically induced,  drug therapy
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Antihypertensive Agents; 31828-71-4/Mexiletine; 4205-90-7/Clonidine; 51322-75-9/tizanidine; EC P-450 CYP1A2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The Safety of H2-Blockers Use During Pregnancy.
Next Document:  Analysis of Drug Interactions Involving Fruit Beverages and Organic Anion-Transporting Polypeptides.