DISCREPANCY BETWEEN PLASMA LEVEL OF INTRAVENOUSLY INFUSED KANAMYCIN AND ITS NEUROMUSCULAR BLOCKING ACTION IN ANESTHETIZED RATS

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In our previous study on aminoglycoside antibiotic-induced skeletal neuromuscular blockades, we have reported that kanamycin sulfate (KM) has more preferential presynaptic antireleasing action of acetylcholine than gentamicin and neomycin 1-3) and the calcitonin-induced hypocalcemia potentiates presynaptically KM-induced neuromuscular blockade2, 4).In the train of these studies, we noticed that there was a discrepancy between the total infused dose of KM and the strength of its pharmacological actions.When continually and intravenously infused a solution of lower concentration of KM, much higher infused dose was required to induce the same extent of neuromuscular blockade than that of higher concentration.Although this might be explained by the rapid renal elimination rate of the infused KM, there arised a question of KM pharmacokinetics in its plasma levels and its tissue levels probably implicating its properpharmacological actions (neuromuscular and cardiovascular depressions): The plasma level can directly express the tissue level in continual infusion of KM? This question led us to examine the interrelations of the infusion rate, the concentration of infused solutions, the plasma level and the neuromuscular blocking action of KM.