Pharmacokinetics and Pharmacodynamics of Metocurine in Humans with and without Renal Failure

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Abstract
The pharmacodynamics and pharmacokinetics of metocurine were studied in 5 neurosurgical patients with normal renal function, and in 5 anephric patients during and after a renal transplant. After a single i.v. dose of metocurine (0.3 mg/kg), measurements of serum levels and urinary excretion were made using a specific radioimmunoassay for metocurine. Evoked compound electromyographic (ECEMG) response of the thumb adductor to supramaximal stimulation of the ulnar nerve was studied. In the patients for renal transplant, plasma clearance of metocurine was significantly reduced (0.38 vs. 1.2 ml/kg per min, P < 0.01) and the elimination half-life was significantly prolonged (11.4 vs. 6.0 h, P < 0.01). The higher serum concentration of metocurine in patients for renal transplant was accounted for by the absence of renal excretion and a reduced total volume of distribution (0.353 vs. 0.472 l/kg, P < 0.05). The mean serum metocurine concentration necessary for 90% inhibition of the ECEMG was 2.3 times greater in patients undergoing renal transplant than in patients undergoing craniotomy, 1.05 vs. 0.46 .mu.g/ml (P < 0.01). Although serum metocurine concentrations were still high at the end of the renal transplants, reversal of the neuromuscular blockade was possible. Metocurine appears to be an acceptable neuromuscular blocking agent for patients in renal failure although no major advantage over d-tubocurarine and pancuronium could be found.