Pharmacokinetics of Edrophonium and Neostigmine When Antagonizing d-Tubocurarine Neuromuscular Blockade in Man

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Abstract
The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with those of neostigmine in surgical patients anesthetized with halothane and N2O. After an i.v. injection of d-tubocurarine (0.3 mg/kg), the single twitch tension was allowed to return to 5% of the control level. Edrophonium, 0.5 or 1.0 mg/kg (n = 12), or neostigmine, 0.07 mg/kg (n = 6) was then given i.v. in combination with atropine, 1.0 mg, as a 2 min controlled infusion. Train-of-4 and single twitch tensions were followed for 60 min in all patients. Twelve patients were monitored for 90 min, 6 for 120 min, 4 for 150 min and 2 for 240 min. Blood was sampled intermittently for 4 h and assayed for edrophonium or neostigmine using high-pressure liquid chromatography. Edrophonium antagonized the d-tubocurarine blockade. Twitch tension rapidly increased to a plateau (a rate of increase in twitch tension of < 2% of control/min) which was sustained in all cases. The mean time to plateau for edrophonium was 2.9 .+-. 0.21 (.+-. SE) min as compared to 6.1 .+-. 0.75 min for neostigmine. Neuromuscular blockade did not reappear in any patient. The degree of antagonism of the neuromuscular blockade by neostigmine and edrophonium was significantly different. Except for a longer distribution half-life (t1/2) the pharmacokinetic variables for edrophonium did not differ significantly from those for neostigmine. The elimination t1/2 of edrophonium and neostigmine were 110 .+-. 34 min (mean .+-. SD) and 77 .+-. 47, respectively. Edrophonium, 0.5-1.0 mg/kg, has pharmacokinetic variables comparable to neostigmine and produces prompt, sustained and effective antagonism of d-tubocurarine neuromuscular blockade.