Document Detail

Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers.
MedLine Citation:
PMID:  22943633     Owner:  NLM     Status:  MEDLINE    
AIM: The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9).
METHODS: A 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co-treatment with BBJ.
RESULTS: BBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50 ) of less than 2%, but without evidence of mechanism-based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre-incubation, consistent with mechanism-based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration-time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03).
CONCLUSION: The increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9.
Michael J Hanley; Gina Masse; Jerold S Harmatz; Paul F Cancalon; Gregory G Dolnikowski; Michael H Court; David J Greenblatt
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  75     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-09-20     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1041-52     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Anthocyanins / analysis
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
Beverages / adverse effects*,  analysis
Blueberry Plant / adverse effects*,  chemistry
Buspirone / pharmacokinetics*
Citrus paradisi / adverse effects,  chemistry
Cytochrome P-450 CYP3A / antagonists & inhibitors
Drug Interactions
Fluconazole / pharmacology
Flurbiprofen / pharmacokinetics*
Food-Drug Interactions*
Microsomes, Liver / drug effects,  metabolism
Middle Aged
Phenols / analysis
Psoralens / analysis
Grant Support
Reg. No./Substance:
0/Anthocyanins; 0/Phenols; 0/Psoralens; 5GRO578KLP/Flurbiprofen; 8VZV102JFY/Fluconazole; EC Hydrocarbon Hydroxylases; EC protein, human; EC protein, human; EC P-450 CYP3A; TK65WKS8HL/Buspirone

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