Journal Article

Uptake and Effect of Praziquantel and the Major Human Oxidative Metabolite, 4-Hydroxypraziquantel, by Schistosoma japonicum

Ji-qing, You, Catto, Brian A., Shu-hua, Xiao, Hui-fang, Guo

1991

Overview

After exposure to praziquantel in vitro at a concentration of 1 µg/ml for 0.5-2 hr, amounts of praziquantel in Schistosoma japonicum varied from 2.1 ± 1.2 to 3.7 ± 1.6 ng/male worm and 1.3 ± 1.2 to 2.2 ± 1.5 ng/female worm during the time studied. At 30 µ/ml, praziquantel amounts were 11-33-fold higher. However, within 2 hr after removal from a medium containing 30 µg/ml praziquantel, 95% of the drug was released from the parasites. When S. japonicum worm pairs were incubated in vitro with 1, 10, and 30 µg/ml of 4-hydroxypraziquantel, the major human oxidative metabolite of praziquantel, 0.2 ± 0.2, 3.8 ± 1.3, and 7.4 ± 1.3 ng/worm pair, respectively, were found after a 2-hr incubation, 15-30-fold lower than corresponding worm pair amounts of praziquantel. In vivo, when 4- or 5-wk S. japonicum-infected mice were treated orally with praziquantel (300 mg/kg), peak concentrations of praziquantel in plasma determined by high pressure liquid chromatography were 14.7 ± 1.5 µ/ml (4-wk infection) and 16.7 ± 2.8 µg/ml (5-wk infection) 15 min after treatment. Corresponding in vivo worm praziquantel amounts were 1.8 ± 0.4 ng/male worm and 2.4 ± 1.1 ng/female worm, respectively, in the 4-wk infection and 4.6 ± 1.6 ng/male worm and 5.6 ± 1.2 ng/female worm in the 5 -wk infection. Peak plasma concentrations of 4-hydroxypraziquantel were similar but corresponding in vivo worm amounts were 1-20-fold lower, depending on the time after drug administration. In S. japonicum, 4-hydroxypraziquantel was not formed from praziquantel in vitro, but the metabolite had similar pharmacologic effects on S. japonicum worms, e.g., contraction, and tegumental vesiculation, but at a 30-fold higher concentration of drug. Thus, it is unlikely that adequate plasma levels of metabolite are attained after appropriate doses of praziquantel to have a significant antischistosomal effect in S. japonicum-infected mice.

• Publisher: American Society of Parasitologists
• Subject: Animals / Cercariae / Dosage / Drug Action / Female / Infections / Liquids / Male / Metabolic diseases / Mice / Parasitic diseases / Parasitology / Pharmacokinetics / Pharmacology / Praziquantel - analogs & derivatives / Praziquantel - metabolism / Praziquantel - pharmacokinetics / Praziquantel - pharmacology / Praziquantel - therapeutic use / Schistosoma japonicum - drug effects / Schistosoma japonicum - metabolism / Schistosomiasis japonica - drug therapy / Schistosomiasis japonica - metabolism