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The effects of gestational age (GA) and plasma protein concentrations on the plasma protein binding of fentanyl and alfentanil were studied in preterm and term neonates. Binding experiments were performed using split-cell equilibrium dialysis. Fentanyl and alfentanil concentrations were measured using specific radioimmunoassay, and the proteins albumin and alpha-1-acid glycoprotein (AAG) were measured using radial immunodiffusion assays. In the preterm neonates, 77% of fentanyl and 65% of alfentanil was bound. In the term neonates, 70% of fentanyl and 79% of alfentanil was bound. The binding ratio of alfentanil showed a positive correlation with gestational age and AAG concentration. The binding ratio of fentanyl showed a weak, negative correlation with gestational age. These data indicate that fentanyl and alfentanil are not interchangeable at the GA studied because of age-related changes in protein binding.

Cimetidine increases the duration of action of succinylcholine several-fold by an unknown mechanism. The hydrolysis rate of succinylcholine by human plasma was measured with a modified spectrophotometric assay. At a concentration of 1-50 micrograms/ml cimetidine did not inhibit the hydrolysis of succinylcholine. It is concluded that cimetidine may have an effect at the neuromuscular junction but does not inhibit plasma cholinesterase.

The in vitro rates of metabolism of mivacurium chloride and succinylcholine in pooled human plasma were compared. In addition, the rate of metabolism of mivacurium in buffered solutions of butyrylcholinesterase (E.C. 3.1.1.8) and acetylcholinesterase (E.C. 3.1.1.7) was determined. Succinylcholine concentrations were measured spectrophotometrically, and mivacurium concentrations were determined with a high-pressure liquid chromatographic assay. The hydrolysis of mivacurium in plasma followed first-order kinetics, and the rate of hydrolysis decreased as plasma was serially diluted. The Michaelis-Menten constant (Km) for mivacurium metabolism in plasma was 245 mumol/L, and the maximum velocity (Vmax) was 50 U/L; the Km for succinylcholine was 37 mumol/L, and Vmax was 74 U/L. At comparable multiples of the Km the hydrolysis rate of mivacurium was 70% of that of succinylcholine. Mivacurium was metabolized significantly in solutions containing butyrylcholinesterase, but only minimally in solutions containing acetylcholinesterase.