Document Detail

Effects of gender and moderate smoking on the pharmacokinetics and effects of the CYP1A2 substrate tizanidine.
MedLine Citation:
PMID:  17955229     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: We studied the effects of gender and smoking on the pharmacokinetics and effects of the cytochrome P450 (CYP) 1A2 substrate tizanidine. METHODS: Seventy-one healthy young volunteers (male and female nonsmokers, male smokers) ingested 4 mg tizanidine. Plasma concentrations and pharmacodynamics of tizanidine were measured, and a caffeine test was performed. RESULTS: Among nonsmokers, the peak concentration (C(max)) and area under concentration-time curve from 0 to infinity [AUC(0-infinity)] of tizanidine did not differ significantly between females and males. However, the half-life (t(1/2)) was 9% shorter in female nonsmokers than in male nonsmokers (P < 0.05). In male smokers, the t(1/2) was 10% shorter and the weight-adjusted AUC(0-infinity) 33% smaller than in male nonsmokers (P < 0.05). The caffeine/paraxanthine ratio was 35-40% smaller (P = 0.001) in male smokers than in nonsmoking males or females, but did not differ between males and females. Tizanidine lowered blood pressure and caused drowsiness significantly (P < 0.05) more in females than in either male groups. The effects on blood pressure were smallest in male smokers (P < 0.05). CONCLUSIONS: Gender by itself seems to have no clinically significant effect on the pharmacokinetics of tizanidine, whereas smoking reduces plasma concentrations and effects of tizanidine. Any possible effect of gender and smoking is largely outweighed by individual variability in CYP1A2 activity due to genetic and environmental factors and in body weight. Careful dosing of tizanidine is warranted in small females, whereas male smokers can require higher than average doses.
Janne T Backman; Marika T Schröder; Pertti J Neuvonen
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-23
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  64     ISSN:  1432-1041     ISO Abbreviation:  Eur. J. Clin. Pharmacol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-08     Completed Date:  2008-05-28     Revised Date:  2008-06-06    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  17-24     Citation Subset:  IM    
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
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MeSH Terms
Adrenergic alpha-Agonists / adverse effects,  pharmacokinetics*
Area Under Curve
Blood Pressure / drug effects
Body Weight
Caffeine / pharmacokinetics
Clonidine / adverse effects,  analogs & derivatives*,  pharmacokinetics
Cytochrome P-450 CYP1A2 / metabolism*
Drug Interactions
Sex Factors
Sleep Stages / drug effects
Smoking / adverse effects*
Theophylline / pharmacokinetics
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 4205-90-7/Clonidine; 51322-75-9/tizanidine; 58-08-2/Caffeine; 58-55-9/Theophylline; 611-59-6/1,7-dimethylxanthine; EC protein, human; EC P-450 CYP1A2

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

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