Effects of liquid and freeze-dried grapefruit juice on the pharmacokinetics of praziquantel and its metabolite 4'-hydroxy praziquantel in beagle dogs

Effects of liquid and freeze-dried grapefruit juice on the pharmacokinetics of praziquantel and its metabolite 4'-hydroxy praziquantel in beagle dogs
anuary 2003
M. Giorgi, V. Meucci, E. Vaccaro, G. Mengozzi, M. Giusiani and G. Soldani
Pharmacological Research Volume 47, Issue 1 , January 2003, Pages 87-92
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Abstract
Grapefruit juice changes the pharmacokinetic parameters of a variety of drugs metabolized primarily by cytochrome P450 3A. In a three-phase crossover study, six male beagle dogs were administered 100 ml of water (control), 100 ml of commercial liquid grapefruit juice, or 10 g of freeze-dried grapefruit juice (equivalent to 100 ml of liquid grapefruit juice) with 100 ml of water, followed after 2 h by single oral dose of praziquantel (30 mg kg-1). After treatment, the dogs were sampled at different times. Determination of praziquantel and its metabolite 4'-hydroxy praziquantel (identified by GC/MS) was performed by HPLC. Liquid and freeze-dried grapefruit juice pre-administration increased the Cmax of praziquantel about three-fold and the AUC 2.5- and 2.3-fold, respectively. The Tmax (0.75 h) was unaffected by liquid or freeze-dried grapefruit juice, while T1/2 was 2.3- and 1.7-fold higher compared with controls. The amount of 4'-hydroxy praziquantel was also affected by both liquid and freeze-dried grapefruit juice administration: the AUC and Cmax increased four- and three-fold, respectively and the Tmax was significantly enhanced.
These findings demonstrate that both freeze-dried grapefruit juice and commercial liquid grapefruit juice significantly increase plasma concentrations and T1/2 of praziquantel in dogs.