Pharmacokinetic and pharmacodynamic profile of high dose extended intervalpiperacillin-tazobactam

A multiple-dose, open-labelled, randomized, two period crossover human volu nteer study was performed (i) to describe the pharmacokinetic profile and s afety profile of piperacillin and tazobactam (PIT) administered 6.0/0.75 g and 8.0/1.0 g q12h and (ii) to characterize the pharmacodynamic profile of these regimens against a variety of common targeted pathogens. Blood sample s were collected after the third dose and concentrations of P/T were determ ined by a validated high-performance liquid chromatography assay. Pharmacok inetic profiles of P/T were determined by non-compartment analysis. Percent age time above the MIC (%T > MIC) of piperacillin was calculated for a rang e of MICs. In this study, no adverse events were attributed after multiple administrations of either 6.0/0.75 g or 8.0/1.0 g dose regimens. The peak c oncentration, half-life and area under the curve (AUC(0-tau)) of piperacill in were significantly different by a paired t-test (P < 0.05) between the t wo study regimens. The trough concentration, half-life and area under the c urve (AUC(0-tau)) of tazobactam were substantially different from parameter s reported previously for conventional regimens. The 8.0/1.0 g regimen prov ided 50% T > MIC for MICs less than or equal to 32 mg/L, while a similar va lue for the 6.0/0.75 g regimen was less than or equal to 16 mg/L. High-dose P/T regimens with extended interval were well tolerated and provide adequa te dynamic exposure for a variety of susceptible pathogens.