Abstract

To obtain more insight in the relationship between physicochemical properties of neuromuscular blocking agents (NMBAs) and their pharmacokinetic characteristics, a series of 12 aminosteroidal NMBAs, supplemented with data on five related NMBAs from the literature, was investigated in anaesthetized cats. After i.v. bolus injection, plasma concentration decreased very rapidly, showing a biphasic pattern, with half-lives ranging from 0.4 to 1.4 min, and from 3 to 10 min, respectively. Clearance was in the range from 24 to 58 ml · min⁻¹ · kg⁻¹. Compounds containing an acetyl-ester group at position 3 were partly metabolized to the 3-OH derivative. The urinary excretion of the parent drug and metabolites amounted to <10% for each of the compounds. The parent drugs were excreted in large amounts into bile, along with smaller amounts of 3-OH derivatives. The terminal half-life of the urinary and biliary excretion rate were markedly longer than the apparent terminal half-life in plasma, ranging from 11 to 40 min, and from 119 to 489 min in urine and bile, respectively. Lipophilicity of the NMBAs, expressed as the partition coefficient octanol/Krebs (log P), was found to be correlated positively with unbound plasma clearance and unbound initial plasma clearance, and negatively with plasma half-life, volume of distribution at steady state, and mean residence time. The increase of the unbound plasma clearance with increasing lipophilicity is counteracted by the concurrent increase in plasma protein binding.