Journal article
Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
British journal of clinical pharmacology, Vol.75(4), pp.1041-1052
04/2013
Handle:
https://hdl.handle.net/2376/108147
PMCID: PMC3612722
PMID: 22943633
Abstract
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.
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Details
- Title
- Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
- Creators
- Michael J Hanley - Sackler School of Graduate Biomedical SciencesGina Masse - Sackler School of Graduate Biomedical SciencesJerold S Harmatz - Sackler School of Graduate Biomedical SciencesPaul F Cancalon - Tufts UniversityGregory G Dolnikowski - Tufts Medical CenterMichael H Court - Sackler School of Graduate Biomedical SciencesDavid J Greenblatt - Sackler School of Graduate Biomedical Sciences
- Publication Details
- British journal of clinical pharmacology, Vol.75(4), pp.1041-1052
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Number of pages
- 12
- Grant note
- United States Highbush Blueberry Council National Institute of General Medical Sciences, National Institutes of Health (R01 GM 061834) Wild Blueberry Association of North America National Institutes of Health (F31 AT 006068)
- Identifiers
- 99900547212401842
- Language
- English
- Resource Type
- Journal article