Effect of bile duct obstruction on the biliary secretion of meropenem in rats

Abstract

Background: The biliary secretion of antibiotics decreases proportionately to an increase in intrabiliary pressure. The aim of this study was to evaluate the effect of bile duct obstruction on biliary secretion of meropenem. Material and Methods: 110 Wistar albino rats were used in this study. There were 11 groups each including 10 rats. In groups A1, B1, C1, D1, E1 and F, the common bile ducts were ligated for 7 days. In the control groups (A2, B2, C2, D2 and E2), sham surgery was performed. A single dose of 14 mg/kg of meropenem was infused intravenously for 10 min. The serum concentration of meropenem was measured 30 min later in groups A1 and A2, 1 h later in groups B1 and B2, 2 h later in groups C1 and C2, 4 h later in groups D1 and D2 and 6 h later in groups E1 and E2. In group F, the intrabiliary pressure was measured in situ on day 7 for confirmation. Results: The biliary / serum level ratio of meropenem in the obstructed rats within 30 min, 1, 2, 4 and 6 h of infusion was 163, 113, 67, 36 and 28%, respectively. The biliary/serum level ratio of meropenem in the control rats within 30 min, 1, 2, 4 and 6 h of infusion were 302, 149, 123, 127 and 126%, respectively. Conclusion: Compared to the control rats, the biliary levels of meropenem was reduced in the obstructed rats compared to control rats. However, the measured levels were greater than the minimum inhibitory concentration (MIC). After conduction of clinical studies, meropenem may be an ideal agent in the treatment of acute cholecystitis and cholangitis caused by obstruction of the biliary tract.