title: 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)
authors.affiliation: Department of Anaesthesiology, University Hospital Leiden, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Gesink-van der Veer
authors.forename: A G
authors.initials: AG
authors.lastname: Burm
authors.forename: A A
authors.initials: AA
authors.lastname: Vletter
authors.forename: J G
authors.initials: JG
authors.lastname: Bovill
mesh_terms: D000328:Adult; D015760:Alfentanil / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000771:Anesthesia, Intravenous; D003424:Crohn Disease / Q000378:metabolism* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007422:Intestines / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism
chemical_list: D009961:Orosomucoid; D015760:Alfentanil