Prolonged Analgesia After Epidural Injection of a Poorly Soluble Salt of Fentanyl

Epidurally administered fentanyl is commonly used in postoperative pain management. The onset of action is rapid, but the duration of analgesia is short. In this study we examined the hypothesis that a poorly soluble 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 epidural fentanyl citrate (FC) and fentanyl pamoate (FP) were studied in white male Sprague-Dawley rats. Somatic and visceral nociceptive stimulation (tail flick and colorectal distension, respectively) were used to test the analgesic effects of the drugs. The calculated dose producing 100% of the maximum possible effect (100% MPE) for FP was 31μg toward somatic and 33μg toward visceral noxious stimulation, and for FC it was 3 jag toward both stimulations. The antinociceptive effects were similar, with 31μg of FP and 3μg of FC. The areas under the time-response curves (AUC) were significantly higher with FP than with FC when high doses (5μg of FC or 50μg of FP) were used, but with doses expected to produce 100% MPE, differences between the study drugs were not observed in the duration of analgesia. We conclude that the duration of antinociceptive effect of fentanyl can be prolonged when administered as a poorly soluble salt.