Document Detail

Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine.
MedLine Citation:
PMID:  8728348     Owner:  NLM     Status:  MEDLINE    
A prospective cohort study was conducted to examine the effects of double-strength grapefruit juice on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics of terfenadine in poor metabolizers of terfenadine. Six healthy volunteers who were previously found to be poor metabolizers of terfenadine were studied, with each participant serving as his or her own control. In phase I of the study, terfenadine was given to participants at recommended dosages until steady state was achieved (60 mg twice daily for 7 days). In phase II, participants began receiving concomitant twice-daily, double-strength servings of grapefruit juice for 7 days. Serial pharmacokinetic and pharmacodynamic determinations were made after each phase of the study. The main outcome measures were serum concentrations of terfenadine and terfenadine acid metabolite, and corrected QT intervals as determined by 12-lead electrocardiogram. Significant changes occurred in time to maximum concentration (t(max)) and area under the concentration-time curve (AUC) of terfenadine and terfenadine acid metabolite after addition of grapefruit juice. All participants had detectable concentrations of unmetabolized terfenadine at the end of Phase I, which were quantified in three of the six participants. Further, all participants had increased and quantifiable levels of unmetabolized terfenadine after addition of grapefruit juice that were associated with prolongation of the QT interval relative to the baseline control period without terfenadine. Grapefruit juice did not alter the elimination half-life (t1/2) of terfenadine acid metabolite. Because of the intraindividual variability in the pharmacokinetics of terfenadine, further study is needed to confirm these results.
P K Honig; D C Wortham; A Lazarev; L R Cantilena
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  36     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-09-30     Completed Date:  1996-09-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  345-51     Citation Subset:  IM    
Division of Clinical Pharmacology of the Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
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MeSH Terms
Biological Availability
Cohort Studies
Electroencephalography / drug effects
Food-Drug Interactions*
Histamine H1 Antagonists / blood,  pharmacokinetics*
Middle Aged
Prospective Studies
Terfenadine / blood,  pharmacokinetics*
Grant Support
FDA 224-88-3006/FD/FDA HHS
Reg. No./Substance:
0/Histamine H1 Antagonists; 50679-08-8/Terfenadine

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

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