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Comparative Pharmacokinetics of d-Tubocurarine and Metocurine in Man.

Meijer, D. K. F. Ph.D.; Weltering, J. G.; Vermeer, G. A. M.D.; Scaf, A. H. J. Ph.D.

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To compare the pharmacokinetics of 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 intravenous administration of d-tubocurarine, 0.15 mg/kg (five patients), and metocurine, 0.05 mg/kg (five patients), in patients anesthetized with thiopental and nitrous oxide for cholecystectomy. Plasma disappearances 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 hours after injection ranged from 46 to 95 per cent of the dose for d-tubocurarine and from 46 to 58 per cent 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 hours 11.8 and 2.1 per cent of the doses were excreted in bile, respectively. The observed differences in total-body clearances and volumes of distribution (V1) may be partly explained by greater protein binding of d-tubocurarine. The results indicate that biliary excretion is an alternative route of elimination for d-tubocurarine only. Also, d-tubocurarine is less dependent on renal excretion for its elimination, and probably is preferable to metocurine for use in patients with renal failure.
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