Bioequivalence and pharmacokinetics characteristics of clozapine sustained release tablets in Beagle dogs

AIM:To study the oral relative bioavailability and pharmacokinetics of clozapine sustained release tablets in Beagle dogs.METHODS:The self-crossover design was conducted in 6 Beagle dogs.A single dose of clozapine sustained release tablets 100mg and clozapine generic tablets 100 mg were taken orally in group A and B,respectively.Plasma clozapine levels were determined by a reversed-phase HPLC method.The pharmacokinetic parameters were analyzed by non-compartmental method.RESULTS:The pharmacokinetic parameters were as follows:tmax,Cmxa,t_(1/2)and AUC_(0-1)were(7.3±s1.0)h,(986±274)μg.L~(-1),(8.1±1.4) h,(17452±5618)μg.h.L~(-1)for clozapine sustained-release tablets and(3.3±0.8)h,(1388±346)μg·L~(-1),(9.5±1.0)h,(14174±3420)μg.h.L~(-1)for clozapine generic tablets.Compare with clozapine generic tablets,relative bioavailability of clozapine sustained-release tablets was(120±28)% based on AUC_(0-1).There was significant difference between two preparations(P0.05).CONCLUSION:Clozapine sustained-release tablet shows prolonged-action characteristics and its bioavailability is better than clozapine generic tablet.