Pharmacokinetics and pharmacodynamics of metocurine in humans with and without renal failure.
The pharmacodynamics and pharmacokinetics of metocurine were studied in five neurosurgical patients with normal renal function, and in five anephric patients during and following a renal transplant. Following a single intravenous 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 also studied. In the patients for renal transplant, plasma clearance of metocurine was significantly reduced (0.38 vs. 1.2 ml . kg-1 . min-1, P less than 0.01) and the elimination half-life was significantly prolonged (11.4 vs. 6.0 h, P less than 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 less than 0.05). The mean serum metocurine concentration necessary for 90 per cent inhibition of the ECEMG was 2.3 times greater in patients undergoing renal transplant than in patients undergoing craniotomy, 1.05 vs. 0.46 microgram/ml (P less than 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.
D000328:Adult; D003399:Craniotomy; D005071:Evoked Potentials; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D016030:Kidney Transplantation; D007700:Kinetics; D014403:Tubocurarine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D014459:Ulnar Nerve / Q000187:drug effects
C032943:metocurine; D014403:Tubocurarine