No 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.

A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples were taken during a period of 12 h, and praziquantel concentration was measured by high-performance liquid chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during a period of 12 h; they increased 100% when cimetidine was jointly administered. Compared with other regimens, the high levels obtained and the longer duration of action seem to be advantageous in prolonging the exposure of the parasites to the drug and support previous clinical experience showing that the treatment of neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with the drug still retaining its cysticidal properties. Moreover, simultaneous administration of praziquantel and cimetidine could improve further the efficacy of the single-day therapy for cysticercosis and other parasitic diseases, such as schistosomiasis.