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

Abstract

Since little is known about the mechanism of biliary excretion of cationic drugs, biliary excretion of erythromycin was studied in rats. Infusion of sulfobromophthalein and taurocholate significantly decreased biliary erythromycin excretion, whereas infusion of dibromosulfophthalein, cefpiramide, ursodeoxycholate-3-O-glucuronide and taurolithocholate-3-sulfate had no effect on biliary excretion of erythromycin. Vinblastine significantly inhibited biliary erythromycin excretion. Phenothiazine treatment significantly increased biliary erythromycin excretion. However, erythromycin infusion did not affect biliary vinblastine excretion. These findings indicate a multiplicity of biliary excretory pathways for organic cations; at least one additonal pathway may exist for organic cations apart from P-glycoprotein.

Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats

“…[ 14 C]Taurolithocholate‐3‐sulfate and BSP were infused at the rate of 0.2 µmol/min/100 g for 60 or 90 min, which is twice the excretory maximum of these compounds (approximately 0.1 µmol/min/100 g) 24,25 . ICG was infused at the rate of 20 nmol/min/100 g for 120 min, which is above its excretory maximum (approximately 10 nmol/min/100 g), and [ 14 C]EM was infused at the rate of 0.1 µmol/min/100 g for 90 min 19 . Bile samples were collected every 10 min, and the concentration of various compounds was measured using radioactivity determined by a liquid scintillation counter, or measured spectrophotometrically with OD 580 after alkalization for BSP and OD 805 for ICG.…”

“…In the present study, in order to systematically evaluate the effect of colchicine on the biliary excretion of cholephilic compounds, we studied the effect of colchicine on the biliary excretion of substrates of various canalicular transporters, which were administered at or beyond their excretory maximum in rats. The substrates that were administered were: TC, cholate (CA) and TUDC as Bsep substrates, taurolithocholate‐3‐sulfate (TLCS) and sulfobromophthalein (BSP) as Mrp2 substrates 17,18 and erythromycin (EM) as a P‐gp substrate 19 . Furthermore, the effect of colchicine on the biliary excretion of indocyanine green (ICG), the excretory mechanism of which is unknown, 20 was also studied.…”

Biliary excretion of azelnidipine, a calcium antagonist, in rats

“…Phenothiazine (5 mg/100 g dissolved in 0.28 mL corn oil) was intraperitoneally injected to SD rats for 3 days prior to the experiments, 11,12 and the biliary [ 14 C]azelnidipine excretion was studied as described above. Phenothiazine of this dose was reported to increase the expression of P‐gp, 11 and increased the biliary excretion of vinblastine in the authors’ previous report 12 …”

Biliary excretion of taurocholate, organic anions and vinblastine in rats with α‐naphthylisothiocyanate‐induced cholestasis

“…The aim of the present study was to simultaneously examine the effect of a single dose of ANIT on the biliary excretion of typical substrates of the canalicular transporters and on the amount of these transporters in rats. Taurocholate (TC) was used as a Bsep substrate, 3 leukotriene C 4 (LTC 4 ) and pravastatin were used as substrates of Mrp2, 15–17 and vinblastine (VLB) was used as a substrate of P‐gp 18 …”