Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. An example of a complex study covering both tolerance and pharmacokinetics.

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.