Derendorf H, Dalla Costa T
College of Pharmacy, University of Florida, Gainesville 32610, USA.
Int J Clin Pharmacol Ther. 1996 Nov;34(11):482-8.
The pharmacokinetics of piperacillin, tazobactam and its M1 metabolite were studied in patients with various degrees of renal impairment after single and multiple intravenous administration of a fixed piperacillin/tazobactam combination. It could be shown that creatinine clearance is an excellent predictor for the pharmacokinetics of all 3 compounds. Piperacillin and tazobactam concentrations can be adjusted by applying prolonged dosing intervals in renal patients. Whereas in the case of piperacillin and tazobactam, renal impairment affects only the elimination of these drugs, in the case of M1 it also has an effect on the formation. In patients with decreased renal function, less tazobactam is excreted renally and, hence, more is available for metabolism. At the same time, renal elimination of M1 is impaired leading to increased M1 plasma concentrations. An equation is derived that allows prediction of the resulting M1 levels based on creatinine clearance. The magnitude of the measured and calculated M1 concentrations are well predictable and much lower than those observed in animal toxicity studies. Therefore, it can be assumed that after prolongation of the dosage intervals resulting M1 plasma concentrations should be safe.
