Sustained-release praziquantel tablet: pharmacokinetics and the treatment of clonorchiasis in beagle dogs

Abstract

Praziquantel is rapidly absorbed and secreted; and thus fractional doses are recommended for the treatment of cestode and trematode infections. In the present study, we developed a new praziquantel tablet formula allowing sustained-release (SRP). In vitro dissolution of SRP tablets showed that praziquantel at 300 mg/tablet combined with hydroxypropyl methylcellulose dissolved completely at a constant rate over 10 h, whereas the conventional praziquantel tablet (PZQ) was only 40% dissolved. Pharmacokinetic studies in dogs confirmed that SRP was absorbed more slowly than PZQ. The mean value of the area under the concentration/time curve from 0 h to the final observation time, the maximum concentration in serum, and the time of maximum concentration in serum for SRP were 3,471,500 ng/min for 0.25 ml, 10,300 ng for 0.25 ml, and 192 min, while the values for PZQ were 688,600 ng/min for 0.25 ml, 2,500 ng for 0.25 ml, and 135 min. The cure rate in dogs with a heavy infection (500 metacercariae) treated with a single dose of SRP (150 mg/tablet) at 50 mg/kg was 80%, while in dogs treated with a single dose of SRP (300 mg/tablet) at 30 mg/kg it was 60%, and the cure rate with PZQ was 20%. In each case, the egg reduction rate was similar (over 90%). No abnormal liver functions or hepatic or renal pathologies were observed in dogs administered with SRP at 30 mg/kg. The SRP tablet showed sustained release and slow absorption; and it had an improved anthelmintic efficacy against Clonorchis sinensis in experimental dogs, compared with conventional praziquantel.