Effects of liquid and freeze-dried grapefruit juice on the pharmacokinetics of praziquantel and its metabolite 4'-hydroxy praziquantel in beagle dogs.
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 preadministration increased the C(max) of praziquantel about three-fold and the AUC 2.5- and 2.3-fold, respectively. The T(max) (0.75 h) was unaffected by liquid or freeze-dried grapefruit juice, while T(1/2) 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 C(max) increased four- and three-fold, respectively and the T(max) was significantly enhanced. These findings demonstrate that both freeze-dried grapefruit juice and commercial liquid grapefruit juice significantly increase plasma concentrations and T(1/2) of praziquantel in dogs.
Giorgi
M
M
Pharmacology and Toxicology Section, Department of Veterinary Clinics, University of Pisa, V.le delle Piagge 2, 56124 Pisa, Italy. mgiorgi@vet.unipi.it
Meucci
V
V
Vaccaro
E
E
Mengozzi
G
G
Giusiani
M
M
Soldani
G
G
D000818:Animals; D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry* / Q000378:metabolism*; D004285:Dogs; D005612:Freeze Drying / Q000379:methods; D008297:Male; D011223:Praziquantel / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
D011223:Praziquantel