PHARMACOKINETICS OF PIPERACILLIN, TAZOBACTAM AND ITS METABOLITE IN RENAL IMPAIRMENT

The pharmacokinetics of piperacillin, tazobactam and its M1 metabolite were studied in patients with various degrees of renal impairment aft er single and multiple intravenous administration of a fixed piperacil lin/tazobactam combination. It could be shown that creatinine clearanc e is an excellent predictor for the pharmacokinetics of all 3 compound s, Piperacillin and tazobactam concentrations can be adjusted by apply ing prolonged dosing intervals in renal patients. Whereas in the case of piperacillin and tazobactam, renal impairment affects only the elim ination of these drugs, in the case of M1 it also has an effect on the formation. Ln 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 increase d M1 plasma concentrations. An equation is derived that allows predict ion of the resulting M1 levels based on creatinine clearance, The magn itude of the measured and calculated M1 concentrations are well predic table and much lower than those observed in animal toxicity studies, T herefore, it can be assumed that after prolongation of the dosage inte rvals resulting M1 plasma concentrations should be safe.