REMIFENTANIL PHARMACOKINETICS IN OBESE VERSUS LEAN PATIENTS

Background: Remifentanil is a short-acting opioid whose pharmacokineti cs have been characterized in detail. However, the impact of obesity o n remifentanil pharmacokinetics has not been specifically examined. Th e goal of this study was to investigate the influence of body weight o n remifentanil pharmacokinetics.Methods: Twelve obese and 12 matched l ean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were c ollected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-c ompartment model to the concentration versus time curves. Nonlinear mi xed-effects population models examining the influence of lean body mas s (LBM) and total body weight (TBW) were also constructed. Clinical si mulations using the final population model were performed. Results: Th e obese patient cohort reached substantially higher remifentanil conce ntrations. The individual pharmacokinetic parameters of a two-compartm ent model were not significantly different bem een the obese versus le an cohorts (unless normalized to TBW). The final population model scal ed central clearance and the central and peripheral distribution volum es to LBM. The simulations illustrated that remifentanil pharmacokinet ics are not grossly different in obese versus lean subjects and that T BW based dosing in obese patients can result in excessively high remif entanil concentrations. Conclusions: The essential findings of the stu dy are that remifentanil's pharmacokinetics are not appreciably differ ent in obese versus lean subjects and that remifentanil pharmacokineti c parameters are therefore more closely related to LBM than to TBW. Cl inically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.