Effect of experimentally-induced hepatic cirrhosis on the pharmacokinetics of orally administered praziquantel in the rat.
The effects of pretreatment with the hepatotoxin, thioacetamide, on the pharmacokinetics of praziquantel, a broad spectrum schistosomicidal agent with a high hepatic clearance, were studied in male Wistar rats. Animals were pretreated with either thioacetamide (25 mg in 100 ml of drinking water, n = 5) for 24 weeks or received plain drinking water (n = 5) over the same period. After the treatment period, praziquantel was administered orally (25 mg/kg as a 20 mg/ml solution in PEG 200) as a single dose. Blood samples (0.3 ml) were collected from the clipped tail at various times up to 4 h post administration. Plasma was analysed for praziquantel using an HPLC method. Mean peak plasma praziquantel concentrations were approximately 1.0 mg/l for both groups. The time to reach peak concentrations, and post-peak elimination half-life, were approximately 0.7 h and 1.0 h, respectively, for both groups. Similarly, mean AUC was approximately 2.0 mg.h/l for both groups. Statistical comparisons indicated that there were no significant differences in the pharmacokinetic parameters estimated in the two groups of animals. It was concluded that thioacetamide-induced hepatic cirrhosis has no effect on the pharmacokinetics of orally administered praziquantel in the rat, at the dose level studied.
Kokwaro
G O
GO
Welsh School of Pharmacy, University of Wales College of Cardiff, UK.
Taylor
G
G
D000284:Administration, Oral; D000818:Animals; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011223:Praziquantel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D013853:Thioacetamide / Q000633:toxicity
D013853:Thioacetamide; D011223:Praziquantel