Journal of Antimicrobial Chemotherapy, Vol 42, 769-778, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
T Dalla Costa, A Nolting, A Kovar and H Derendorf
The investigation of tissue penetration and distribution of antibiotics is
of great importance, since infections occur mostly in the tissues. The aim
of this study was to investigate the pharmacokinetics of piperacillin and
tazobactam, alone and in combination, by measuring total plasma and free
interstitial concentrations, and to examine the relationship between free
levels of both drugs in blood and those in the extracellular space.
Piperacillin and tazobactam were administered, alone and in combination, to
anaesthetized rats as a single iv bolus dose. Total plasma concentrations
and free extracellular concentrations were quantified by HPLC. In-vivo
microdialysis sampling was used to study the free tissue distribution
patterns of both drugs. The pharmacokinetics of piperacillin and tazobactam
in plasma were consistent with a two-compartment body model. Piperacillin
pharmacokinetics were not influenced by co-administration of tazobactam.
Tazobactam's volumes of distribution and clearance were decreased by the
co-administration of piperacillin and the area under the curve was
significantly increased. Comparisons between calculated free concentrations
in the peripheral compartment for both drugs and measured free
extracellular concentrations revealed excellent agreement. For piperacillin
and tazobactam, alone and in combination, predictions of the
concentration-time profiles of free drug in the peripheral compartment can
be made on the basis of plasma data.
Determination of free interstitial concentrations of piperacillin- tazobactam combinations by microdialysis [In Process Citation]
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, 32610, USA.
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