Alcuronium: a pharmacodynamic and pharmacokinetic update.

Alcuronium may be considered a muscle relaxant of historical rather than clinical significance. However, recent information from the manufacturer revealed its persisting clinical use in 26 countries worldwide. Thus, a pharmacodynamic-pharmacokinetic update appears mandatory. An intravenous (IV) single-bolus injection of alcuronium (0.25 mg/kg = ED95) was administered to 10 patients undergoing maxillofacial surgery during nitrous-oxide opioid anesthesia. Alcuronium neuromuscular block (evoked twitch tension), plasma concentration, and renal elimination (high-performance liquid chromatography [HPLC] assay) were measured during the 12-h after its administration. The time of onset, the time from end of injection to recovery to 25% of control twitch tension (DUR25%), and the recovery index were 2.2 +/- 1.2, 54 +/- 14, and 37 +/- 11 min, respectively (mean +/- SD). Two hours after the injection of alcuronium, partial recovery from the neuromuscular block had occurred from 100% to 26% +/- 24% depression of twitch tension, although less than 25% of the injected dose was recovered from the urine. The 12-h plasma concentration and urinary recovery were 0.1 +/- 0.08 mg/L (one-sixth of the 50% inhibitory concentration) and 61% +/- 20%, respectively. Recovery from neuromuscular block was dominated by intercompartmental distribution rather than by renal elimination. Since alcuronium does not undergo biodegradation, our data may serv as a reference for the complex pharmacokinetics of readily metabolized modern muscle relaxants. The long plasma half-life with slow excretion merits attention with respect to the erroneous original perception that alcuronium was an intermediate-acting muscle relaxant.

Kinetics of intercompartmental disposition and excretion of tubocurarine, gallamine, alcuronium and pancuronium in patients with normal and impaired renal function.

Pharmacokinetic data of tubocurarine, gallamine, alcuronium and pancuronium in patients with normal and without renal function are taken from the literature. They are adapted to an open three compartment pharmacokinetic model, and the proportional intercompartmental distribution is calculated as a function of time from 1 min to 8 h. All drugs show similar kinetic properties: During the first 10 min rapid disappearance from compartment 1 results in saturation of compartment 2. Maximum saturation of compartment 3 is achieved after 1 to 2 h followed by a gradual disappearance of the relaxants from the whole system. 20-25% of the dose undergo sequestration apart from intercompartment equilibrium. In normal individuals sequestration is observed after 2 to 3 h whereas in anuric patients it is already demonstrated during the first hour. Intercompartmental redistribution is the basic principle governing the pharmacodynamic profile of all of the four drugs if given in clinical dosage.