Pharmacokinetics of intravenous camazepam in dogs

Free plasma concentrations were studied after i.v. administration of three different doses (2.5, 5, 7.5 mg/kg respectively) of 3-N,N-dimethylcarbamoyloxy-7-chloro-5-phenyl-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (camazepam) to three healthy male mongrel dogs. Total plasma concentration was measured by a specific gas-liquid chromatography technique. The protein binding of camazepam in dog plasma was studied by using the equilibrium dialysis method and found to vary from 88.5 to 76.7% when the total drug concentration increased from 8 ng/ml to 8 micrograms/ml. For the subsequent pharmacokinetic analysis the calculated free camazepam plasma concentrations were used. The superposition principle was applied to each dog demonstrating that a linear pharmacokinetic model was applicable. Computer analysis showed that the pharmacokinetics of camazepam could be conveniently described by a three-compartment model assuming that the drug elimination occurred from the central compartment exclusively. The half-life of the terminal elimination phase ranged from 6.4 to 10.5 h, a finding which might suggest that camazepam could exhibit long-lasting effects.