Journal article
Grapefruit juice, lyophilized grapefruit juice, and powdered whole grapefruit inhibit cytochrome P450 mediated triazolam hydroxylation by beagle dog liver microsomes
Journal of veterinary pharmacology and therapeutics, Vol.33(2), pp.189-195
04/2010
Handle:
https://hdl.handle.net/2376/108099
PMCID: PMC6195767
PMID: 20444044
Abstract
Coadministration of grapefruit juice has been proposed to enhance the systemic availability and decrease the required dose of drugs such as cyclosporine that are extensively metabolized in the intestine and liver. Although grapefruit juice inhibits human cytochrome P450 (CYP) 3A, effects on dog CYP have not yet been reported. Consequently, we determined whether grapefruit juice (GFJ) inhibits triazolam hydroxylation by Beagle dog liver microsomes (DLM) using human liver microsomes (HLM) as positive control. Results were compared to effects of lyophilized GFJ and commercially-available powdered grapefruit capsules, which may be more convenient dosage forms. GFJ inhibited α-hydroxytriazolam formation in both DLM and HLM with similar IC
50
values of 0.56 and 0.52% (v/v), respectively. Lyophilized GFJ and powdered grapefruit also inhibited DLM α-hydroxytriazolam formation with IC
50
values of 0.76 and 1.2 mg / mL, respectively. Consistent with mechanism-based enzyme inhibition, preincubation of DLM with any of the grapefruit products for 20 minutes resulted in significant enhancement of inhibition of triazolam α-hydroxylation by 8 to 20%. The results indicate that 16 grams of lyophilized GFJ or 23 grams of powdered grapefruit would be equivalent to dosing 100 mL of GFJ.
In vivo
pharmacokinetic interaction studies are needed to confirm these
in vitro
findings.
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Details
- Title
- Grapefruit juice, lyophilized grapefruit juice, and powdered whole grapefruit inhibit cytochrome P450 mediated triazolam hydroxylation by beagle dog liver microsomes
- Creators
- Michael J Hanley - Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MassachusettsRosario Cerundolo - Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PennsylvaniaNoel Radwanski - Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PennsylvaniaMichael H Court - Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts
- Publication Details
- Journal of veterinary pharmacology and therapeutics, Vol.33(2), pp.189-195
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Identifiers
- 99900546737901842
- Language
- English
- Resource Type
- Journal article