PHARMACOKINETICS AND PHARMACODYNAMICS OF REMIFENTANIL IN PERSONS WITHRENAL-FAILURE COMPARED WITH HEALTHY-VOLUNTEERS

Background: Remifentanil is an opioid analgesic for use in anesthesia. An ester linkage renders it susceptible to rapid metabolism by blood and tissue esterases. Thus it was hypothesized that remifentanil elimi nation would be independent of renal function. Because its principal m etabolite (GR90291) is eliminated renally, it would depend on renal fu nction. This study was designed to evaluate the pharmacokinetics and p harmacodynamics of remifentanil and its metabolite in persons with and without renal failure. Methods: Two groups of volunteers received two -stage infusions of remifentanil: low dose with 0.0125 mu g . kg(-1). min(-1) for 1 h followed by 0.025 mu g . kg(-1). min(-1) for 3 h; and high dose with 0.025 mu g . kg(-1). min(-1) for 1 h followed by 0.05 m u g . kg(-1). min(-1) for 3 h. Blood samples were collected for analys is of remifentanil and GR90291 concentrations. The pharmacokinetics of remifentanil were fit using a one-compartment pharmacokinetic model. Remifentanil's effect was determined intermittently using minute venti lation during a hypercapnic (7.5% CO2) challenge. Results: Fifteen pat ients with renal failure and eight control participants were enrolled. The clearance and volume of distribution of remifentanil were not dif ferent between those with renal failure and the controls. Patients wit h renal failure showed a marked reduction in the elimination of GR9029 1; the half-life of the metabolite increased from 1.5 h in the control s to more than 26 h in patients with renal failure. The steady-state c oncentration of GR90291 is likely to be more than 25 times higher in p ersons with renal failure. There were no obvious differences in opioid effects on minute ventilation in the controls and in patients with re nal failure. Conclusions: The pharmacokinetics and pharmacodynamics of remifentanil were not altered in patients with renal disease, but the elimination of its principal metabolite, GR90291, was markedly reduce d. Based on simulations, the concentration of GR90291 at the end of a 12-h remifentanil infusion of 2 mu g . kg(-1). min(-1) is not likely t o produce significant opioid effects.