Microdialysis study of biliary excretion of chloramphenicol and its glucuronide in the rat

The biliary excretion of chloramphenicol and its glucuronide has been evaluated by use of a microdialysis probe linked to automatic on-line microbore high-performance liquid chromatography. The microdialysis probe was inserted into the bile duct between the liver and the duodenum; to avoid obstruction of the bile duct or bile salt waste, a shunt linear probe was used. After intravenous administration of chloramphenicol succinate (100 mg kg(-1)) the amounts of unbound chloramphenicol and its glucuronide in the bile microdialysate were recorded. According to the pharmacokinetic results disposition of chloramphenicol seems to fit a two-compartment model whereas that of chloramphenicol glucuronide fits a one-compartment model in rat bile. The area under the concentration-time curve for chloramphenicol glucuronide was twice that for chloramphenicol in rat bile duct. Clearance of chloramphenicol glucuronide was significantly higher than that of chloramphenicol in biliary excretion, indicating that chloramphenicol and its glucuronide are actively excreted into the bile.