Narcotic effects on hepatic disposition of sulfobromophthalein in rats

Ascending morphine doses above 5 mg/kg s.c. progressively reduced plasma clearance of sulfobromophthalein (BSP) and raised hepatic levels of this dye in rats. The narcotic reduced the elimination constant of BSP without affecting its volume of distribution. Because abdominal surgery markedly reduced plasma clearance of BSP, no further effect of morphine could be shown in rats with bile cannulas. In duct-cannulated animals morphine had no effect on BSP concentration in bile, but did raise hepatic BSP levels while reducing bile flow and biliary BSP content. The narcotic also lowered the biliary transport maximum of BSP. The effects on BSP disposition were demonstrated acutely after morphine administration but had subsided completely by 1 and 2 days after giving narcotic. The present findings suggest that morphine impaired the secretion of BSP into bile by a mechanism not involving biliary occlusion and thereby enhanced retention of this dye in liver and plasma.