The effects of oral diazepam pretreatment on the biliary excretion of sulfobromophthalein in rats.
Studies were performed with rats to examine the effects of single, as well as repetitive oral diazepam (DZP) pretreatment on biliary sulfobromophthalein (BSP) excretion rates and on bile flow parameters. One-hour pretreatment of male rats with 150 mg/kg of DZP resulted in about a one-third reduction in the peak biliary excretion rate of BSP (60 mg/kg, iv) and this was associated with a decrease in relative proportions of conjugated BSP in bile. The biliary excretion of preconjugated BSP was unaffected. BSP hepatic uptake and storage were apparently unaffected. In vitro DZP markedly inhibited BSP conjugating activity. In contrast to the above results, when BSP excretion was examined 1 h after the last of five daily oral doses of DZP (150 mg kg-1 day-1), no change in the peak elimination rate of this dye was evident. However, bile flow rates were higher in DZP-treated rats than in controls. When rats were examined 24 h after the last of five daily oral doses of DZP (150 mg/kg), the choleretic response persisted. Further studies showed that the repetitive DZP pretreatment enhanced the bile salt-independent mechanisms of bile formation.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002756:Cholagogues and Choleretics; D003975:Diazepam / Q000494:pharmacology*; D004896:Erythritol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D013448:Sulfobromophthalein / Q000378:metabolism*; D013997:Time Factors
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D013448:Sulfobromophthalein; D005978:Glutathione; D003975:Diazepam; D004896:Erythritol