Ss. Sorooshian et al., PHARMACOKINETICS AND PHARMACODYNAMICS OF CISATRACURIUM IN YOUNG AND ELDERLY ADULT PATIENTS, Anesthesiology, 84(5), 1996, pp. 1083-1091
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.