ISOBOLOGRAPHIC ANALYSIS OF THE INTERACTION BETWEEN EPIDURAL SUFENTANIL AND BUPIVACAINE IN RATS

The present study was performed to evaluate the nature of the interact ion between epidurally administered sufentanil and bupivacaine in prod ucing antinociception in rats. Rats in which epidural catheters had be en inserted received epidural injections with bupivacaine and sufentan il. Nociception was tested by use of the tail-withdrawal reaction (TWR ) test and the hot-plate test. Isobolographic analyses were performed with fixed and variable dose ratio treatment schedules based on the ED (50)s and the highest inactive concentrations of the compounds in both tests. In the TWR test, a synergistic interaction was obtained betwee n the two compounds independent of whether a variable dose ratio regim en (with either 0.08 mu g/rat sufentanil or 80 mu g/rat bupivacaine as the preset component) or a fixed dose ratio of 1/1,000 sufentanil/bup ivacaine (based on the individual ED(50)s) was used. In the hot-plate test, a synergistic interaction was observed only in the variable dose ratio regimen with 0.08 mu g/rat sufentanil as the preset component a nd in the fixed dose ratio regimen of 1/1,000 sufentanil/bupivacaine ( a ratio based on the ED50 values of the TWR test) but not with a ratio of 1/200, as demonstrated by the ED(50)s Of both drugs in the hot-pla te test. The interaction between epidurally administered bupivacaine a nd sufentanil seems to be synergistic for both tests when variable and fixed dose ratios are used. The synergism could be more easily demons trated in the TWR test. For drugs with a segmental action,the hot-plat e test seems to be less optimal. The necessity of a minimal critical a mount of bupivacaine to obtain synergism may have clinical implication s. (C) 1997 Elsevier Science Inc.