| Abstract: | Complexation of various equipotent doses of fentanyl-like opioids in hydroxypropyl-β-cyclodextrin (HP-β-CD) results in a potentiation of the spinal activity of these opioids after both epidural and intrathecal administration in a fixed diluent volume of 10 μl. The first active and mot optimal concentrations of HP-β-CD after epidural administration differed between the opioids and varied from 1 to 20% HP-β-CD. The duration of deep surgical analgesia increased at optimal concentrations of HP-β-CD with a factor 3 for fentanyl (15% HP-β-CD), 3.6 for sufentanil (5–10% HP-β-CD), respectively. Increasing the concentrations of HP-β-CD above these optimal concentrations did not further potentiate the analgesic activity of the opioids. The complexation of the opioids in HP-β-CD also increased the duration of supraspinal side-effects. However, except for lofentanil, the potentiations of the analgesic activity were always longer lasting than those for the secondary side-effects. As a consequence, there was a gain in the total time of analgesia without side-effects. After intrathecal administration, there was no gain in the duration of deep surgical analgesia after complexation of fentanyl, carfentanil and alfentanil in HP-β-CD. For both sufentanil and lofentanil, maximal potentiation of analgesia was measured at 10% HP-β-CD with, respectively, 2.8- and 1.7-fold increases in the duration of analgesia. Also intrathecally, there was some gain in the duration of duration of analgesia without supraspinal side-effects. These results on the potentiation of the opoids with HP-β-CD are discussed in relation to the lipophilicity of the tested opioids. © 1993 Wiley-Liss, Inc. |
