A PHARMACOKINETIC APPROACH TO RESOLVING SPINAL AND SYSTEMIC CONTRIBUTIONS TO EPIDURAL ALFENTANIL ANALGESIA AND SIDE-EFFECTS

A pilot study was conducted in 7 normal volunteers to demonstrate the feasibility of employing pharmacokinetic tailoring to achieve matching plasma opioid concentration-time curves after epidural (e.p.) and int ravenous (i,v.) alfentanil administration. Each subject participated i n 1 pretest and 2 test sessions, Our pain model was cutaneous electric al stimulation of the finger and toe, adjusted to produce a baseline p ain report of 5 (strong pain on a 0-5 scale). On test day 1, subjects received e.p, alfentanil (750 mu g) and an i.v. saline infusion. Seria l measurements of analgesia, end tidal CO2, pupil size, subjective sid e effects, and plasma alfentanil concentrations were conducted before and at various time intervals over a 4-h period after alfentanil admin istration. On test day 2, subjects received e.p, saline and a pharmaco kinetically tailored i.v, infusion (using individual pharmacokinetics determined on the pretest day) designed to achieve a plasma concentrat ion-time profile identical to that observed on the epidural day, The s ame battery of effect measurements was administered as on the Ist test day. Plasma alfentanil was measured to verify the accuracy of the tai lored infusion, Plasma alfentanil concentration profiles were nearly i dentical on both test days. Peak plasma alfentanil concentrations were near the reported minimum effective analgesic concentration (MEAC), O verall, analgesia was slightly greater with e.p, administration, Onset of pain relief was rapid, and duration was approximately 1.5 h with e .p. and 1 h with i.v. alfentanil. There were no differences in pupil s ize, ETCO(2), or subjective side effects between e,p. versus i,v. admi nistration. We conclude that a 750 mu g dose of e,p, alfentanil produc es plasma drug concentrations within the analgesic range and that syst emic redistribution from the epidural space appears to account for mos t, but not all, of the analgesia. Side effects appear to be due to sys temic absorption of the opioid. There may be little clinical benefit t o e,p. administration at doses which result in plasma alfentanil conce ntrations near the MEAC.