Therapeutic doses of erythromycin esteolate is not cholestatic in rats in vivo
The effect of erythromycin esteolate (EE) on bile flow and bile acid secretion was studied in male Wistar rats in vivo. Daily oral treatment with a dose of up to 100 mg/kg for 1 week increased the bile flow and the bile acid secretion. Increasing the days of treatment to 4 weeks with a dose of 20 mg/kg did not alter the measured parameters significantly. Acute intravenous injection of erythromycin lactobionate (50 mg/kg) also increased bile flow and biliary bile acid secretion temporarily. The increase in bile flow may partly be due to the osmotic effect of the drug and its metabolites in bile. Since EE failed to produce cholestasis in the range of therapeutic doses, rats do not seem to be a suitable experimental model for studying EE-cholestasis.
Key wordsErythromycin esteolate Bile flow Bile acid secretion
Unable to display preview. Download preview PDF.
- Anwer MS, Kroker R, Hegner D (1975) Bile acid secretion and synthesis by isolated rat hepatocytes. Biochem Biophys Res Commun 64:603–609Google Scholar
- Boyer JL (1971) Canalicular bile formation in the isolated perfused rat liver. Am J Physiol 221:1156–1163Google Scholar
- Chelvan P, Hamilton-Miller JMT, Brumfitt W (1979) Biliary excretion of erythromycin after parenteral administration. Br. J Clin Pharmacol 8:233–235Google Scholar
- Dujovne CA (1978) Hepatotoxic and cellular uptake interactions among surface active components of erythromycin preparations. Biochem Pharmacol 27:1925–1930Google Scholar
- Kendler J, Anuras S, Laborda O, Zimmerman HJ (1972) Perfusion of the isolated rat liver with erythromycin esteolate and other derivatives. Proc Soc Exp Biol Med 139:1272–1275Google Scholar
- Kroker R, Anwer MS (1979) Altered biliary secretion of bile acids as a possible reason for drug-induced intraphepatic cholestasis. Naunyn-Schmiedeberg's Arch Pharmacol 308:R49Google Scholar
- Murphy PJ, Williams TL, McMahon RF, Marshal FJ (1975) Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of propionyl erythromycin moiety in the rat. Drug Metab Dispos 3:155–163Google Scholar
- Plaa GL, Priestly BG (1977) Intrahepatic cholestasis induced by drugs and chemicals. Pharmacol Rev 28:207–273Google Scholar
- Robinson MM (1962) Demonstration by “challenge” of hepatic dysfunction associated with propionyl erythromycin ester lauryl sulfate. Antibiot Chemother 12:147–151Google Scholar
- Stephens VC, Pugh CT, Davis NE, Hoehn MM, Ralston S, Sparks MC Thompkins L (1969) A study of the behavior of propionyl erythromycin in blood by a new chromatographic method. J Antibiot 22:551–557Google Scholar
- Viteri AL, Green JF, Jr, Dyck WP (1979) Erythromycin ethyl-succinate-induced cholestasis. Gastroenterology 76:1007–1008Google Scholar