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Pancuronium, vecuronium and pipecuronium are quaternary ammonium steroidal neuromuscular blocking agents. These drugs are typical nondepolarizing muscle relaxants. The steroidal compounds and/or their metabolites have been determined using mass spectrometry or gas chromatography. In this review, these analytical methods and application of the methods to pharmacokinetics are introduced.

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular blocking and circulatory actions of pipecuronium bromide (PPB) were evaluated in patients under halothane-nitrous oxide-oxygen anesthesia in comparison with those of pancuronium bromide (PCB) in a multi-center cooperative study. Twitch tension of the adductor pollicis muscle was elicited by supramaximal stimulation of the ulnar nerve every 10 seconds. The study was performed according to the following 4 steps and the results were obtained. 1) Cumulative administration of 0.01 mg.kg-1 of PPB or PCB resulted in the potency ratio of 1.3:1.0 and the dose response curves of the two agents paralleled with each other. 2) With PPB 0.05 mg.kg-1 or 0.1 mg.kg-1, almost 100% block of the twitch was obtained. Both duration of action and the recovery time were shorter with 0.05 mg.kg-1 group. 3) After the first dose of 0.04 mg.kg-1 when the twitch recovered to 25% of the initial height 0.02 mg.kg-1 was given and this was repeated. Intervals between the doses showed large individual differences and no significant change was observed with repeated doses. 4) Safety of the drug. No significant change in heart rate or blood pressure was observed with PPB but with PCB a significant increase in heart rate was observed. The study revealed that PPB is slightly more potent than PCB and the duration of action is longer, but it has no untoward cardiovascular action in man under halothane anesthesia.