Sustained-release praziquantel tablet: pharmacokinetics and the treatment of clonorchiasis in beagle dogs.
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.
Department of Parasitology and Tropical Medicine, and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 110-799, Korea.
Sung-Tae
ST
Hong
Sang Hyup
SH
Lee
Seung-Jin
SJ
Lee
Weon-Gyu
WG
Kho
Mejeong
M
Lee
Shunyu
S
Li
Byung-Suk
BS
Chung
Min
M
Seo
Min-Ho
MH
Choi
D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D003003:Clonorchiasis / Q000188:drug therapy / Q000378:metabolism*; D003004:Clonorchis sinensis / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010273:Parasitic Diseases, Animal / Q000188:drug therapy / Q000378:metabolism*; D011223:Praziquantel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome
D000871:Anthelmintics; D013608:Tablets, Enteric-Coated; D011223:Praziquantel