The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1 X 20 mg/kg, 1 X 50 mg/kg, 3 X 10 mg/kg and 3 X 25 mg/kg body weight (tau = 4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinico-psychological parameters and subjective comments, the largest daily dose tested (3 X 25 mg/kg = 75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1--2 h, and the elimination half-life for the period 2--8 h was 1--1.5 h.

The concentration-time-course in serum as well as the urinary excretion of Praziquantel and metabolites were studied, in healthy volunteers, using the 14C-labelled compound, at dose levels of 14 and 46 mg/kg. The analytical methods applied comprised determination of radioactivity (Praziquantel and metabolites in toto) as well as unmetabolized drug by two specific methods (gas liquid chromatography, fluorometry).Depending on the dose, the concentration maximum of radioactivity in serum was observed 2 to 4 hrs after administration. In contrast, the concentration maximum of the unmetabolized drug was attained at 1 to 2 hrs after administration. Compared to the concentrations of 14C-radioactivity, the concentrations of unmetabolized drug were smaller by a factor of about 10 2, indicating rapid and almost complete metabolism of Praziquantel.The radioactivity was eliminated from serum with a half life of approx. 4 hours whereas the half life of unmetabolized drug was found to be approx. 1.5 hours.On the basis of the radioactivity values, 84±3% of the 14 mg/kg dose and 80±6% of the 46 mg/kg dose were found to be excreted renally within 4 days. More than 90% of the renally excreted drug was recovered within the first 24 hours.The excretion data indicate a virtually complete enteral absorption of the drug.

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