Comparative pharmacokinetics of BB-K8 and kanamycin in dogs and humans

Abstract

Comparative studies in beagle dogs suggested that the pharmacokinetic profiles of BB-K8 and kanamycin are similar. After intravenous (iv) administration to dogs, BB-K8 and kanamycin were rapidly distributed in plasma and tissue fluids; their "apparent" volumes of distribution comprised approximately 23% of the total body volume. Like kanamycin, BB-K8 had a plasma half-life of about 0.8 h which paralleled the urinary excretion rate. Approximately 92% of the dose was excreted as unchanged drug within 6 h of dosing, and clearance appeared to be primarily by glomerular filtration. After intramuscular (im) administration to dogs, BB-K8 and kanamycin were totally and rapidly absorbed; peak concentrations in the plasma occurred 0.5 to 1.0 h after dosing. The kinetic parameters governing the distribution and elimination of BB-K8 and kanamycin after an im dose were similar to those obtained for iv dosing and indicate desirable dose-independent kinetics. A human pharmacokinetic study indicated that the kinetic profiles of BB-K8 and kanamycin are similar in man after im dosing. Like kanamycin, BB-K8 is rapidly absorbed, yielding peak serum concentrations of about 20 mug/ml at 1 h after a 500-mg im dose. The plasma half-life of these two drugs was approximately 2.3 h. Clearance in man was primarily by glomerular filtration, and the urinary excretion of BB-K8 and kanamycin accounted for 83% of the dose.