Plasma levels of piperacillin and vancomycin used as prophylaxis in liver transplant patients.

The pharmacokinetics of piperacillin and vancomycin used intravenously as antibioprophylaxis were measured in the plasma and bile during orthotopic liver transplantation. Piperacillin (4 g and then 2 g every 4 h) and vancomycin (1 g and then 0.5 g every 6 h) were infused in 10 patients. During vascular clamping without venovenous bypass, clearance of both antibiotics decreased in relation to renal insufficiency. During the surgical procedure, volume of distribution of both drugs increased because of fluid redistribution. The peaks of piperacillin after first, second and third administrations were respectively 314, 265 and 210 mg.l-1, while trough levels were 46.5, 55.2 and 54.5 mg.l-1. The peaks of vancomycin were 54.4, 49.6 and 40.9 mg.l-1, while first and second trough levels were 9.5 and 12 mg.l-1. These plasma concentrations were quite similar to levels reported in healthy subjects despite large blood loss and fluid replacement. However, piperacillin trough concentrations (< 64 mg/l) were too low in relation to its concentration-dependent antibacterial activity and vancomycin peak concentrations (> or = 40 mg/l) were slightly too high in relation to its toxicity.