Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes

Abstract

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.

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

“…Praziquantel has a short half life, thus decreasing the drug plasma level (Leopold et al 1978) would decrease the frequency of adverse effects. The 2 h interval between drug intake proved difficult to manage in field conditions.…”

Disseminated muscular cysticercosis with myositis induced by praziquantel therapy.

“…11,12 Most investigators have reported good tolerability of praziquantel. 13,14 Some patients present some side effects including fever, headache, nausea, vomiting, dizziness, meningismus, increased intracranial pressure, 11,12 and cerebral infarct. These adverse reactions are probably not due to a toxic effect of praziquantel but rather to an inflammatory reaction produced by the host in response to massive destruction of cysticerci in the central nervous system.…”

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

“…Pharmacokinetic data of different doses of PZQ are few and old, and have been obtained in healthy volunteers rather than in schistosome-infected patients (Leopold et al 1978). An exponential increase was found in the area under the curve (AUC) with the PZQ dose in the range of 5 to 50 mg/kg, with a six-fold increase from 20 to 50 mg/kg (Leopold et al 1978). However, these data do not come from infected patients, and hence cannot be extrapolated so easily.…”