Tt. Randell et al., PROLONGED ANALGESIA AFTER EPIDURAL INJECTION OF A POORLY SOLUBLE SALTOF FENTANYL, Anesthesia and analgesia, 79(5), 1994, pp. 905-910
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.