[Pharmacokinetic interpretation of the myorelaxant effect of kanamycin]

Changes in the neuromuscular conductivity and pharmacokinetics of kanamycin in the blood serum were studied in parallel on anesthetized cats treated with the antibiotic administered intravenously in a dose of 85 mg/kg or by means of infusion at a rate of 6.5-8 mg/kg . min. Combination of the logistic equation of the effect kinetics with the bioexponential equation of kanamycin pharmacokinetics resulted in analytical interrelations between the rate of the neuromscular conductivity suppression and kanamycin concentrations in the central and peripheral compartments of the two-compartmental model. The concentration-response curves in the first case were of the same S-shaped form, while in the second case they were of an irregular character. This suggested that the biophase was attributed formally to the central compartment of the model. However, the values of kanamycin concentrations in this compartment corresponding to the same level of the effect at the period of its development was always higher than those for the period of its extinction. This was indicative of the kinetic heterogeneity of the central compartment and biophase. Irrespective of the kanamycin administration regimen, the character of the effect-concentration relationship was the same and the antibiotic blood level determined after intravenous and infusion administration of the drug and corresponding to 50% reduction of the neuromuscular conductivity were close. Administration of kanamycin by means of infusion is more convenient, since it prevents development of undesirable respiration arrest in the animals.