Influence of crohn's disease on the pharmacokinetics and pharmacodynamics of alfentanil

Abstract

We have compared the dose requirements, pharma cokinetics and pharmacodynamics of alfentanil in 12 patients with Crohn's disease and 10 control patients undergoing abdominal surgery. Plasma concentrations of α1-acid glycoprotein (AAG) and alfentanil protein binding were also measured. Anaesthesia was induced with aifentanil 100 μg kg-1 and thiopentone, and maintained with nitrous oxide in oxygen and aifentanil 25-200 μg kg-1 h-1 Arterial blood samples were obtained before and after each change in the aifentanil infusion rate and for 6 h after stopping the infusion. Pharmacokinetic data were derived using non-compartmental methods. Alfentanil concen tration-effect data were evaluated by non-linear regression, where effect was either response or no response to surgical stimulation. Mean intra operative aifentanil requirement was greater in patients with Crohn's disease (2.48 μg kg-1 min-1) than in control patients (1.35 μg kg-1 min-1) (P< 0.01). Mean elimination half-life, total plasma clearance and steady state distribution volume in patients with Crohn's disease were comparable to those in control patients (80 vs 81 min, 5.7 vs 6.4 ml kg-1 min-1 and 0.70 vs 0.68 litre kg-1, respectively). Mean plasma concentration at which the probability of no response was 50% for the intra-abdominal period of surgery was greater in the Crohn group (359 ng ml-1) than in the control group (199 ng ml-1 (P<0.02). Plasma AAG concentrations were greater in the Crohn group, but the free fraction of aifentanil was similar in both groups. This study indicates that the increased alfentanil requirement in patients with Crohn's disease may be attributed to a change in pharmacodynamics. (Br. J. Anaesth. 1993; 71: 827-834) © 1993 British Journal of Anaesthesia.