Biliary Cef piramide Excretion: Its Relation to Biliary Excretion of Bile Acids and Sulfobromophthalein

Abstract

Cefpiramide, a β-lactam antibiotic, has been reported to be excreted from hepatocytes into the bile by a carrier-mediated system. Herein, the relationship of biliary cefpiramide excretion to the excretion of bile acids and sulfobromophthalein was studied in rats. Biliary cefpiramide excretion was markedly inhibited by sulfobromophthalein, lithocholate-3-O-glucuronide and taurolithocholate-3-sulfate, whereas it was not inhibited by ursodeoxycholate or taurocholate. However, the inhibitory effect of cefpiramide on the biliary excretion of sulfobromophthalein or lithocholate-3-sulfate was very small. These findings indicate that, although cefpiramide is excreted by a process common to organic anions and bile acid sulfate and glucuronide, two or more excretory pathways for organic anions exist and cefpiramide has affinity for only one of these carriers.

Effects of Organic Anions and Vinblastine on Biliary Excretion of Erythromycin in Rats

“…CPM and PS significantly increased bile flow to 140 and 190% of that in the control rats, respectively, as previously reported [28,29] (data not shown). Among the organic anions, only BSP significantly decreased biliary EM excretion (table 1).…”

Biliary excretion of olmesartan, an anigotensin II receptor antagonist, in the rat

“…2, Table 1). Bile flow was increased by the infusion of cefpiramide and pravastatin as reported previously (data not shown) 17,18 . In contrast, TC and TUDC did not inhibit biliary excretion of olmesartan in SDR (Fig.…”

“…These results strongly suggest that olmesartan is a substrate of Mrp2. This is further confirmed by the inhibition of the biliary excretion of olmesartan by Mrp2 substrates, BSP, 21 cefpiramide 17 and pravastatin 18,22 . Because only a part of olmesartan in the bile was glucuronidated both in SDR and EHBR, it was hard to compare the affinity of olmesartan and its glucuronide for Mrp2.…”

“…The infusion via the femoral vein of BSP, cefpiramide and pravastatin at the rate of 0.2 µmol/min/100 g and of TC and TUDC at the rate of 1.0 µmol/min/100 g was started just after bile duct cannulation and continued during the experiments in SDR. The infusion rate of organic anions and bile acids were chosen to become their excretory maximum or above according to our previous studies 16–20 …”