PROLONGED ANALGESIA AFTER EPIDURAL INJECTION OF A POORLY SOLUBLE SALTOF FENTANYL

Epidurally administered fentanyl is commonly used in postoperative pai n management. The onset of action is rapid, but the duration of analge sia is short. In this study we examined the hypothesis that a poorly s oluble salt of fentanyl (fentanyl pamoate) would create a depot of the drug in the epidural space and thus provide prolonged analgesia. The dose-response relationship and duration of analgesic action of epidura l fentanyl citrate (FC) and fentanyl pamoate (FP) were studied in whit e male Sprague-Dawley rats. Somatic and visceral nociceptive stimulati on (tail flick and colorectal distension, respectively) were used to t est the analgesic effects of the drugs. The calculated dose producing 100% of the maximum possible effect (100% MPE) for FP was 31 mu g towa rd somatic and 33 mu g toward visceral noxious stimulation, and for FC it was 3 mu g toward both stimulations. The antinociceptive effects w ere similar, with 31 mu g of FP and 3 mu g of FC. The areas under the time-response curves (AUC) were significantly higher with FP than with FC when high doses (5 mu g of FC or 50 mu g of FP) were used, but wit h doses expected to produce 100% MPE, differences between the study dr ugs were not observed in the duration of analgesia. We conclude that t he duration of antinociceptive effect of fentanyl can be prolonged whe n administered as a poorly soluble salt.