Dosage-schedule Independence of d-Tubocurarine Pharmacokinetics and Pharmacodynamics, and Recovery of Neuromuscular Function

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Abstract

To study the relationship of d-tubocurarine (dTc) dosage schedule to its pharmacokinetics and pharmacodynamics, and recovery of neuromuscular function, 30 patients were given markedly different doses of dTc to produce 90 per cent or greater depression of twitch tension for two hours during stable halothane anesthesia. Ten patients each were given dTc in one of three dosage schedules: 20 mg/m2 as a single large bolus; repeated smaller doses of 5 mg/m2; or a continuous infusion. After two hours of neuromuscular blockade, all patients experienced spontaneous recovery to 10 per cent of control twitch tension. Thereafter, five patients in each group continued with spontaneous recovery and five had antagonism of paralysis by neostigmine, 0.25 mg, and atropine, 0.1 mg, every 5 min. Serum dTc concentrations were determined by radioimmunoassay every 30 min and during recovery.

There was no difference among the three dosage protocols in any of the following variables: total dose of dTc (mg/m2/hr) needed for two hours of paralysis and spontaneous recovery to 10 per cent of control twitch tension; time for recovery of twitch tension occurring spontaneously or during antagonism by neostigmine; or total dose of neostigmine needed during antagonism of paralysis. There was a relationship between serum dTc concentration and neuromuscular blockade, which was the same among the three dosage protocols. There was no clinically significant difference in pharmacokinetics among the groups. The authors conclude that there is a relationship between serum dTc concentration and neuromuscular blockade, and that it is independent of dTc dosage administered. Duration of neuromuscular blockade following dTc administration was related to serum dTc concentration and not to initial dTc dosage.

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