Biliary excretion and pharmacokinetics of several fluoroquinolones after intravenous injection in rabbits

Abstract

The aim of this study was to measure the concentrations of enrofloxacin (ERFX) and other fluoroquinolones; orbifloxacin (OBFX), marbofloxacin (MBFX), and ofloxacin (OFLX) in the plasma and bile of rabbits after a single intravenous (IV) injection. Twenty male rabbits were divided into four groups and given each drug by IV injection into the ear vein at a dose of 5.0 mg/kg BW. The concentration of ERFX, ciprofloxacin (CPFX), OBFX, MBFX and OFLX in plasma and bile were determined by HPLC. CPFX, metabolite of ERFX, was also measured by HPLC in plasma and bile of rabbits receiving ERFX. Several pharmacokinetic parameters in plasma were calculated and biliary clearance (CL_bile) was calculated from extent of biliary excretion and accumulation of AUC of each drug. After IV injection, elimination half-life (t_1/2β) was 4.13, 3.68, 6.60, 5.14 hr; volume of distribution at a steady state (V_dss) was 1.24, 0.503, 0.771, 1.02 L/kg; and total body clearance (CL_tot) was 1.05, 0.418, 0.271, 0.453 L/kg/hr, respectively. The values for CL_bile for ERFX, OBFX, MBFX, and OFLX were 0.0048, 0.0050, 0.0057, and 0.0094 L/kg/hr, respectively. These values represent 0.48%, 1.2%, 2.1%, and 2.3% of the total body clearance (CL_tot) of each drug, respectively. The biliary clearance of CPFX was also measured and found to be 0.0199 L/kg/hr with ERFX administration. The results showed that ERFX, OBFX, MBFX, and OFLX were not excreted into the bile to a significant extent, making them safe drugs to use in rabbits.