PHARMACOKINETICS OF PIPERACILLIN AND TAZOBACTAM IN CRITICALLY ILL PATIENTS WITH RENAL-FAILURE, TREATED WITH CONTINUOUS VENOVENOUS HEMOFILTRATION (CVVH)

Objective: Kinetics of piperacillin (pip), in combination with the bet a-lactamase inhibitor tazobactam (taz) have been studied in volunteers and patients in relatively stable conditions. The fixed drug preparat ion appeared to have ideal pharmacokinetic properties if renal functio n was normal or slightly impaired, but no data are available for criti cally ill patients in anuric renal failure. This study should provide such data. Patients, design: We studied the pharmacokinetics in nine p atients with multiple organ failure, including anuric renal failure, t reated with continuous veno-venous hemofiltration (CVVH). Patients rec eived a standard schedule of 4 g pip and 0.5 g taz administered over 0 .5 h intravenously, 8 hourly. During 2 consecutive days, the serum lev els of both compounds were determined, and total clearance (CIT) was c alculated from serum concentrations. Results: All nine patients comple ted day 1, and 8 completed day 2 of the protocol. On day 1, single-dos e kinetics showed considerable spread, but pip/taz serum levels follow ed the pattern as expected, with a pip/taz concentration ratio of 20 : 1. On day 2, however, taz serum concentrations showed a relative incr ease as compared to pip, resulting in a change in the serum pip/taz co ncentration ratio to 10 : 1 on day 2. The CIT of pip was 2.52 +/- 1.38 l/h (t 1/2 : 5.9 +/- 2.9 h), and CIT of taz 4.44 +/- 2.28 l/h (t 1/2 : 8.1 +/- 3.7 h). The CIT and t 1/2 of pip and taz correlated highly s ignificantly with clearance by CVVH. Despite a higher CI, taz has a lo nger half-life, because of a higher volume of distribution. Conclusion : In CVVH dependent patients, pip/taz fixed drug preparations can be u sed initially, but the pip dosage should be increased relative to that of taz (or interval-adjusted) to prevent cumulation of taz, as compar ed to the active antimicrobial agent pip.