Pharmacokinetics and Pharmacodynamics of d-Tubocurarine in Infants, Children, and Adults

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Abstract
The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 mo., n = 7), infants (2-12 mo., n = 7), children (1-12 yr, n = 9) and adults (12-30 yr, n = 8) during 70% N2O, 0.58 MAC [minimum anesthetic concentration] halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained and the EMG [electromyograph] of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurred (Cpss(50) was 0.18 .+-. 0.09 .mu.g/ml in neonates and 0.27 .+-. 0.06 .mu.g/ml in infants, both significantly lower than the values of 0.42 .+-. 0.14 and 0.53 .+-. 0.14 .mu.g/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 .+-. 0.33 1/kg in neonates, significantly greater than the values of 0.52 .+-. 0.22, 0.41 .+-. 0.12 and 0.30 .+-. 0.10 1/kg in infants, children and adults, respectively. The elimination half-life (t.beta.1/2) was 174 .+-. 60 min in neonates, significantly longer than the values of 90 .+-. 23 and 89 .+-. 18 min in children and adults, respectively. Plasma clearance did not differ with age. D50 (obtained by the product of Vdss and Cpss(50) and described as the quantity of drug present at steady-state to produce 50% paralysis) was determined and did not differ between groups. During comparable N2O-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by Cpss(50). Because of the larger Vdss in younger patients, dose size should not differ with age. Because of the longer t.beta.1/2 in neonates, 2nd and subsequent doses should be required at less frequent intervals.