Investigation of mezlocillin disposition with a porcine model.
The suitability of the pig as an animal model for mezlocillin disposition was assessed. Serum, urine, and bile were collected after the administration of 50, 100 and 200 mg kg-1 mezlocillin to pigs and drug pharmacokinetics were characterized. Mezlocillin concentrations in biological fluids were determined by HPLC and free mezlocillin was determined by ultrafiltration. The pharmacokinetics of mezlocillin appeared to be independent of dose over the dosage range studied. Total clearance, renal clearance, and biliary clearance were 0.18 (0.05) 1 h-1 kg-1, 0.13 (0.03) 1 h-1 kg-1, and 0.07 (0.02) 1 h-1 kg-1, respectively. The steady-state volume of distribution was 0.29 (0.08) 1 kg-1. The pharmacokinetic parameters determined in the porcine model are similar to those reported for health human volunteers. Therefore, this model appears suitable for the study of mezlocillin disposition, and may be applied to the study of other agents that are appreciably biliary excreted.