Influence of piperacillin-tazobactam on pharmacokinetics of gentamicin given once daily

The effect of piperacillin-tazobactam on the pharmacokinetics of gentamicin given once daily was studied. Healthy adult volunteers each received four drug regimens in randomized order: gentamicin 7 mg/kg i.v. once daily (1) by itself, (2) with piperacillin 4 g and tazobactam 0.5 g (both as the sodium salt) every six hours i.v., (3) with piperacillin 4 g and tazobactam 0.5 g i.v. every eight hours, and (4) with piperacillin 8 g and tazobactam 1 g by continuous i.v. infusion over 24 hours. All the gentamicin doses were infused over 30 minutes two hours after piperacillin-tazobactam. Blood samples were drawn before and at the end of each gentamicin infusion and at intervals up to 12 hours after the start of each gentamicin infusion. Samples were assayed for gentamicin concentration by an enzyme-multiplied immunoassay technique and for piperacillin and tazobactam concentrations by high-performance liquid chromatography. Six women and four men completed all four drug regimens. For the gentamicin-alone regimen, the mean +/- S.D. area under the concentration-versus-time curve was 78.06 +/- 10.28 micrograms/mL.hr, the mean +/- S.D. peak concentration (30 minutes after the end of an infusion) was 20.28 +/- 2.54 micrograms/mL, and the mean +/- S.D. half-life was 2.41 +/- 0.24 hours. The values for gentamicin alone did not differ significantly from those for gentamicin in any of the combination regimens. Coadministration of once-daily gentamicin and piperacillin-tazobactam in various i.v. infusion regimens did not affect the pharmacokinetics of once-daily gentamicin.