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.
Hong
Sung-Tae
ST
Department of Parasitology and Tropical Medicine, and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 110-799, Korea.
Lee
Sang Hyup
SH
Lee
Seung-Jin
SJ
Kho
Weon-Gyu
WG
Lee
Mejeong
M
Li
Shunyu
S
Chung
Byung-Suk
BS
Seo
Min
M
Choi
Min-Ho
MH
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