Pharmacokinetics and pharmacodynamics of atracurium with and without previous suxamethonium administration

Suxamethonium increases neuromuscular block produced by non-depolarizing agents administered subsequently. To determine if this effect has a pharmacokinetic or pharmacodynamic origin, 18 ASA physical status I or II adults received atracurium 0.2 mg kg-1, with (n = 10) or without (n = 8) previous injection of suxamethonium 1 mg kg-1, during a thiopentone-nitrous oxide-isoflurane (0.5% end-tidal) anaesthetic. Arterial blood samples were obtained and plasma atracurium concentration measured by HPLC. Train-of-four stimulation was applied to the ulnar nerve and the force of contraction of the adductor pollicis muscle was recorded. Mean (SEM) volume of distribution was slightly greater with previous suxamethonium (143 (13) ml kg-1) than without (109 (5) ml kg-1) (P less than 0.04). Mean elimination half-life was unaffected (20.3 (0.8) min and 20.4 (1.6) min, respectively). Neuromuscular block was more intense and recovery was slower with previous administration of suxamethonium. Atracurium concentration at 50% block (Cpss50) was 305 (30) ng ml-1 with and 454 (25) ng ml-1 without previous suxamethonium (P less than 0.01). It is concluded that suxamethonium may be associated with a slight increase in the volume of distribution of atracurium, but this effect is more than compensated by a decrease in atracurium concentration required for a given effect.