PHARMACOKINETICS AND PHARMACODYNAMICS OF CISATRACURIUM IN YOUNG AND ELDERLY ADULT PATIENTS

Background: The effects of a muscle relaxant may differ in elderly com pared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect. M ethods: Thirty-one young (18-50 yr) and 33 elderly (>65 yr) patients a nesthetized with nitrous oxide, isoflurane, and fentanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracuri um was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after su pramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five ven ous blood samples were obtained for plasma drug concentration at inter vals ranging from 2 to 120 min from every patient. Three additional sa mples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concent ration and effect data, The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults. Results: Onset of block was delayed in the elderly; va lues being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2 .4-6.5) min in the young and elderly, respectively (P < 0.01). Duratio n of action was similar in the two groups. Plasma clearance was 319 (2 93-345) ml/min in the study population and did not differ between youn g and elderly patients. Apparent volume of distribution was 13.28 (9.9 -16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respect ively (P < 0.05). There also were differences in pharmacodynamic param eters between the young and elderly; the predominant change being a sl ower rate of biophase equilibration (k(e0)) in the elderly (0.060 [0.0 52-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0 .05). Conclusions: The pharmacokinetics of cisatracurium differ only m arginally between young and elderly adults. Onset is delayed in the el derly because of slower biophase equilibration.