Comparative Pharmacokinetics of d-Tubocurarine and Metocurine in Man

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Abstract
To compare the pharmacokinetics of [the neuromuscular blocking agents] d-tubocurarine and metocurine in man, concentrations of 3H-d-tubocurarine and 14C-metocurine (0,0,N-trimethyl-tubocurarine) in plasma, urine and bile were determined after i.v. administration of d-tubocurarine, 0.15 mg/kg (5 patients), and metocurine, 0.05 mg/kg (5 patients), in patients anesthetized with thiopental and N2O for cholecystectomy. Plasma disappearance of both drugs were triexponential, with mean terminal half-lives of 346 and 217 min for d-tubocurarine and metocurine, respectively. By ion-pair thin-layer chromatography, no metabolite of either compound was found in urine or bile. Renal excretions 48 h after injection were 46-95% of the dose for d-tubocurarine and 46-58% for metocurine. Mean total-body clearances were 56 and 96 ml/min for d-tubocurarine and metocurine, respectively. Biliary elimination of d-tubocurarine was greater than that of metocurine: within 48 h, 11.8 and 2.1% of the doses were excreted in bile, respectively. The observed differences in total-body clearances and volumes of distribution (V1) may be partly due to greater protein binding of d-tubocurarine. Apparently biliary excretion is an alternative route of elimination for d-tubocurarine only. d-Tubocurarine is less dependent on renal excretion for its elimination and probably is preferable to metocurine for use in patients with renal failure.