BACKGROUND Remifentanil is a highly potent opioid with a rapid onset and a short duration of action due to its rapid hydrolysis by esterases in blood and tissues. The major metabolite of remifentanil, GI90291, is much less potent than remifentanil. METHODS The pharmacokinetics of remifentanil and its major metabolite, GI90291, were determined in 24 patients undergoing elective inpatient surgery. Remifentanil was administered as a 1-min infusion (2, 5, 15, and 30 micrograms/kg) after the induction of anesthesia and tracheal intubation. Serial arterial blood samples were collected over 6 h and assayed for remifentanil and GI90291. RESULTS The pharmacokinetics of remifentanil were described using a three-compartment model. Total clearance (250-300 l/h) of remifentanil was independent of dose and was approximately three to four times greater than the normal hepatic blood flow. Volume of distribution at steady state (25-40 l) also was independent of dose. The terminal half-life of remifentanil ranged from 10 to 21 min. Covariate analysis of remifentanil clearance and patient demographics showed that patient body weight, age, and gender did not influence total clearance. This suggests that remifentanil may not need to be dosed according to body weight in adult patients. A simulation was conducted to determine the time required for a 50% reduction in effect site concentration after an infusion designed to maintain a constant effect site concentration. The time required for a 50% reduction in the effect site concentration of remifentanil (3.65 min) was considerably less than that for sufentanil (33.9 min), alfentanil (58.5 min), and fentanyl (262 min). The pharmacokinetics of the major metabolite, GI90291, were independent of the dose of remifentanil. The mean terminal half-life of GI90291 ranged from 88 to 137 min. CONCLUSIONS The pharmacokinetics of remifentanil are consistent with its rapid elimination by blood and tissue esterases; its major metabolite is eliminated more slowly but is not likely to make any significant contribution to the total effect because of its much lower potency. The rapid onset and short duration of action of remifentanil make it well suited for titration of dose (infusion rate) to the desired degree of effect.