Effects of clonidine and IBMX on sulfobromophthalein disposition in rats

Clonidine, an α₂-adrenoceptor agonist, inhibited the biliary excretion, reduced the plasma clearance and increased the hepatic retention of sulfobromophthalein (BSP) in a dose related fashion in rats. The maximal effects of clonidine on BSP disposition occurred about 4 h after pretreatment. The effects of clonidine on biliary excretion and hepatic retention of BSP were retained following laparotomy (with or without bile duct cannulation); however, the effect of clonidine on plasma disappearance profile was not retained following abdominal surgery. Isobutylmethylxanthine (IBMX) affected BSP disposition in a similar fashion as clonidine, in rats without bile duct cannulation only; no effect of IBMX could be observed in bile duct cannulation rats. Yohimbine, an α₂-adrenoceptor antagonist, reversed the effects of clonidine, but not of IBMX, on BSP disposition. It thus seems that clonidine and IBMX exert their effects on BSP disposition by different mechanisms and probably at different sites.