ABSORPTION,DISTRIBUTION AND EXCRETION OF THE SCHISTOSOMICIDE,PYQUITON,IN RABBITS USING BIOLOGICAL ASSAY

After administration of pyquiton (Praziquantel, Embay 8440) to rabbits, the drug was determined directly, either in the biological sample or after extraction of the active compound with chloroform. By placing schistosomes into an aliquot of the diluted biological sample, a criterion is obtained whetherthe concentration of the drug is above or below the threshold that produces stimulation and contraction of the worms. The limit of sensitivity is 0.005 /μg/ml.When pyquiton was injected into various segments of the alimentary canal of rabbits, the drug was best absorbed from the duodenum and ileum, relatively so from the rectum and much less from the colon or stomach. After absorption from the small intestine, the pyquiton plasma level in the peripheral venous blood was about tenfold lower than that in the portal blood.After oral or subcutaneous application of pyquiton at the respective dosages of 100 mg/kg and 20 mg/kg, the plasma levels were about the same. The drug was absorbed rapidly and maximal plasma level was reached within 1 to 1.5 hours. After intramscular injection the concentration of pyquiton in the plasma was higher than that after subcutaneous administration. A rather high plasma level was obtained just after intravenous injection, but the drug was rapidly eliminated from the blood.No accumulation of the drug in plesma was observed when pyquiton was given orally to rabbits once daily for 3 days. With repeated oral doses at 4-hour intervals, distinctly higher dose-dependent plasma levels were obsarved after the second and third doses than after the first.After oral administration to rabbits, pyquiton was rapidly distributed in all organs tested. However, higher concentrations of drug in stomach and small intestine were found 0.5 to 4 hours after administration. It was eliminated in 24 hours from most organs, leaving only trace amounts in stomach and intestine. Biological activity was detectable in rabbits urine and faeces after administration of pyquiton.