Interaction between Grapefruit Juice and Praziquantel in Humans

Abstract

After a single oral dose of praziquantel with 250 ml of grapefruit juice, the area under the concentration-time curve and the maximum concentration in plasma of praziquantel (C max ) were significantly increased (C max for water treatment, 637.71 ؎ 128.5 ng/ml; and C max for grapefruit juice treatment, 1,037.65 ؎ 305.7 ng/ml, P < 0.05). No statistically significant differences were found in the time to maximum concentration of drug in plasma or elimination half-life.Grapefruit juice increases the bioavailability of a variety of drugs (3,4,10,11,13,14,18), but it scarcely affects the elimination half-life (t 1/2 ). These findings suggest that grapefruit juice alters the first-pass metabolism mainly by suppression of the cytochrome P450 enzyme CYP3A4 in the small intestine (1,2,15).Praziquantel is an effective antihelmintic drug, widely used in the treatment of various parasitic diseases, including brain cysticercosis (7,20). It has been shown that the drug undergoes extensive metabolism by cytochrome P450; therefore, the systemic bioavailability of praziquantel is low and variable despite its almost complete gastrointestinal absorption (17). The specific cytochrome P450 enzymes involved in the metabolism of praziquantel in humans have not been characterized (5), but a significant inhibition of praziquantel hydroxylation by compounds that are inhibitors for 3A isoforms of cytochrome P450 has been observed in microsomes isolated from rat liver (16). In previous studies in humans, it was shown that cimetidine (an inhibitor of the microsomal cytochrome P450 mixed-function oxidase system) or simultaneous food administration increased the levels in plasma of praziquantel (6, 12); therefore, the aim of this study was to investigate the effect of the ingestion of grapefruit juice on the pharmacokinetics of praziquantel.Eighteen healthy male volunteers (age range, 23 to 37 years; mean, 28.8 Ϯ 5.4 years) participated in the study. Medical examination before the study showed that they were healthy and had normal results in laboratory tests that included complete blood count, serum chemistry measurement, hepatic test, and urinalysis. The volunteers signed an informed consent after detailed explanation about the purpose and design of the study, as well as the possible risks. The study was approved by the local ethics committee.The study was performed using a balanced randomized crossover design. Volunteers were separated in two groups of nine subjects each and received three tablets of 600 mg of praziquantel (Cisticid; Merck) with 250 ml of water or 250 ml of commercially squeezed grapefruit juice (Florida 7; lot L-2 05:51; Zano Alimentos S.A. de C.V., Mexico City, Mexico).The same lot number was used throughout the study. The interval between tests was 1 week. Blood samples were obtained through an indwelling catheter placed in the antecubital vein at 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, and 8.0 h after the drug administration. Samples were centrifuged; the plasma was separated and stored at Ϫ4°C until an...

Therapy for neurocysticercosis

“…Dexamethasone decreases plasma concentration of PZQ but increases ASOX [26,37]. Food, a high carbohydrate diet, grapefruit juice and cimetidine increase plasma PZQ concentration [26,30,[56][57][58]. Foods rich in fat and cimetidine may also favor ALB absorption.…”

Urinary schistosomiasis

“…Because first pass metabolism is mediated by the cytochrome P450 (CYP) system (e.g. CYP3A4), PZQ may interfere with the hepatic clearance of tacrolimus, cyclosporine and sirolimus [39]. Furthermore, the anti-parasitic effect may be impaired by the concurrent use of intestinal P-glycoprotein inhibitor (e.g.…”

“…chloroquine) and CYP inducers (e.g. rifampin) [39,40]. Serum level may be increased by cytochrome P450 inhibitors, such as ketoconazole and grapefruit juice [39].…”

“…rifampin) [39,40]. Serum level may be increased by cytochrome P450 inhibitors, such as ketoconazole and grapefruit juice [39]. To avoid worsening of the hypersensitivity reaction from the release of egg antigens by the killing of the adult worm, treatment with PZQ should be delayed in patients with Katayama fever.…”

Dificultades diagnósticas y terapéuticas en la neurocisticercosis: presentación de 6 casos y revisión de la literatura

“…La dexametasona disminuye las concentraciones plasmáticas de praziquantel y aumenta las de Asox 39,40 . La dieta rica en carbohidratos, zumo de pomelo y la cimetidina aumentan las concentraciones plasmáticas de praziquantel 6,7,25,38,39 . Las dietas ricas en grasa y la cimetidina pueden también favorecer la absorción del albendazol 20 .…”