The pharmacokinetics of kanamycin were studied in beagle dogs. A parenteral preparation of kanamycin sulphate (5% aqueous solution), which was given at a dosage level of 10 mg/kg of body weight, was the drug product used. The disposition curve which resulted from the intravenous administration of a single bolus dose of the drug was completely described by the biexponential equation:
Cp= 50e-0.1977t+ 36.3e-0.0128t where Cp represents concentration of the drug in the serum at time t (in minutes) and the experimental constants are mean values. Pseudo-distribution equilibrium was rapidly attained and the apparent volumes of the central and peripheral compartments of the two-compartment open model were the same (ca 125 ml/kg). Body clearance (mean ± S.D., n= 6) of kanamycin was 3.21 ±0.72 ml/kg/min. The half-life of the drug was short (58.18 ± 18.43 min) and independent of the route of parenteral (intravenous and intramuscular) administration. Absorption of kanamycin from the intramuscular site was rapid, with a half-time of 9.08 ± 1.10 min. A systemic availability of 89.1 ± 15.8% was obtained. Based on the bioavailability and disposition kinetics a dosage regimen consisting of the intramuscular injection of the dose (10 mg/kg) at 6 h intervals is proposed. An intravenous infusion rate of 48 μg/kgymin is predicted to establish a steady state serum concentration of 15 μg/ml, which is a therapeutic level of the antibiotic for susceptible micro-organisms.
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