Journal article
Effects of powdered whole grapefruit and metoclopramide on the pharmacokinetics of cyclosporine in dogs
American journal of veterinary research, Vol.72(5), pp.687-693
05/2011
Handle:
https://hdl.handle.net/2376/115307
PMID: 21529222
Abstract
To determine whether oral administration of metoclopramide or a commercially available powdered whole grapefruit (PWG) nutraceutical in combination with cyclosporine enhances systemic availability of cyclosporine in dogs.
8 healthy mixed-breed dogs in part 1 and 6 of these 8 dogs in part 2.
Cyclosporine pharmacokinetics were determined over the course of 24 hours after oral administration of cyclosporine (5 mg/kg) alone, cyclosporine with metoclopramide (0.3 to 0.5 mg/kg), cyclosporine with 2 g of PWG, or cyclosporine combined with both metoclopramide and 2 g of PWG by use of a Latin square crossover study with a 14-day washout period between treatments. Sixty days later, 6 of the 8 dogs were given 10 g of PWG followed by cyclosporine, and pharmacokinetic parameters were compared with those previously obtained after administration of cyclosporine alone.
Although metoclopramide or coadministration of metoclopramide and 2 g of PWG had no effect on the pharmacokinetic parameters of cyclosporine, compared with results for cyclosporine alone, the higher (10-g) dose of PWG resulted in 29% faster mean time to maximal plasma cyclosporine concentration, 54% larger area under the curve, and 38% lower apparent oral clearance.
Adjustment of the cyclosporine dose may not be needed when metoclopramide is coadministered orally to prevent common adverse effects of cyclosporine. Powdered whole grapefruit has the potential to reduce the required orally administered dose of cyclosporine but only when PWG is used in an amount (at least 10 g) that is currently not cost-effective.
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Details
- Title
- Effects of powdered whole grapefruit and metoclopramide on the pharmacokinetics of cyclosporine in dogs
- Creators
- Noel E Radwanski - Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. nradwans@yahoo.comRosario CerundoloFrances S ShoferMichael J HanleyMichael H Court
- Publication Details
- American journal of veterinary research, Vol.72(5), pp.687-693
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- United States
- Grant note
- GM-061834 / NIGMS NIH HHS
- Identifiers
- 99900547765001842
- Language
- English
- Resource Type
- Journal article