Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Abstract

In the present study we found that after a single oral dose of 1,800 mg of praziquantel, following a high-lipid diet and a high-carbohydrate diet, the maximum levels in plasma increased 243 and 515% and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271%, respectively.Nine healthy volunteers participated in the study. The mean age was 33.44 years (range, 26 to 47 years), and the mean weight was 72.22 Ϯ 11.29 kg. The protocol was approved by the local ethics committee, and informed written consent was obtained from each subject after detailed explanation of the purpose and risks of the study. Subjects did not take any other medication or alcohol for at least 15 days prior to the study.Volunteers were randomly separated into three groups of three subjects each. Group I received three tablets of 600 mg of praziquantel (1,800 mg) after 10 h of fasting; group II received the same dose of praziquantel immediately after administration of a high-fat diet, and group III received the same dose of praziquantel after a high-carbohydrate diet. Volunteers received a standard lunch 4 h after drug ingestion. The study was repeated in a crossover design allowing 1 week of washout between treatments. Blood samples were obtained through an indwelling catheter placed in the antecubital vein 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 analysis.The high-fat diet consisted of two fried eggs, one slice of ham, orange juice, and milk (200 ml) (protein, 19.63%; fat, 32.44%; and carbohydrate, 47.91%; 656 cal); the high-carbohydrate diet consisted of four tortillas, tomato, chicken (100 g), a slice of white bread, and a glass (200 ml) of orange juice (protein, 15.30%; fat, 10.54%, and carbohydrate, 74.15%; 674.5 cal).Praziquantel in plasma was determined using a high-performance liquid chromatography assay as previously reported (1). The method was linear from 15.6 to 8,000 ng/ml. The limit of quantitation was 15.6 ng/ml. The maximum within-day coefficient of variation was 7.9% at 15.6 ng/ml, and the mean value FIG. 1. Mean concentration in plasma (ϩstandard error of the mean) of praziquantel in healthy volunteers treated with a single oral dose of 1,800 mg (three tablets of 600 mg) during fasting (F) or immediately after a high-fat (‚) or a high-carbohydrate (s) breakfast.

Interaction between Grapefruit Juice and Praziquantel in Humans

“…When comparing our data with those obtained in previous studies, we found that the influence of grapefruit juice on the AUC of praziquantel is comparable to that observed with cimetidine and lower than that observed with food (1.65-and 2.7-fold for AUC, respectively) (6,12).…”

“…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.…”

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.…”

Treatment of urinary schistosomiasis: methodological issues and research needs identified through a Cochrane systematic review

“…This calls for well designed trials incorporating also pharmacokinetic assessment, possibly with sparse sampling and population kinetic assessment. These trials should also control for food intake, as the bioavailability of PZQ depends upon taking it with food and the type of food matters (Mandour et al 1990 ;Castro et al 2000). The rationale behind the widely spaced dosing intervals of metrifonate treatment derives from its long-lasting effect on red blood cells and plasma cholinesterases (Plestina, Davis and Bailey, 1972).…”