Influence of Crohn's disease on the pharmacokinetics and pharmacodynamics of alfentanil.

Abstract

We have compared the dose requirements, pharmacokinetics and pharmacodynamics of alfentanil in 12 patients with Crohn's disease and 10 control patients undergoing abdominal surgery. Plasma concentrations of alpha 1-acid glycoprotein (AAG) and alfentanil protein binding were also measured. Anaesthesia was induced with alfentanil 100 micrograms kg-1 and thiopentone, and maintained with nitrous oxide in oxygen and alfentanil 25-200 micrograms kg-1 h-1. Arterial blood samples were obtained before and after each change in the alfentanil infusion rate and for 6 h after stopping the infusion. Pharmacokinetic data were derived using non-compartmental methods. Alfentanil concentration-effect data were evaluated by non-linear regression, where effect was either response or no response to surgical stimulation. Mean intraoperative alfentanil requirement was greater in patients with Crohn's disease (2.48 micrograms kg-1 min-1) than in control patients (1.35 micrograms 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 alfentanil was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)