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  • Title: Multiple-dose pharmacokinetics of piperacillin and azlocillin in 12 healthy volunteers.
    Author: Tartaglione TA, Nye L, Vishniavsky N, Poynor W, Polk RE.
    Journal: Clin Pharm; 1986 Nov; 5(11):911-6. PubMed ID: 3780161.
    Abstract:
    The pharmacokinetic profile of piperacillin and azlocillin after multiple-dose administration to healthy volunteers was studied. Twelve healthy volunteers received either piperacillin 4 g (as the sodium salt) or azlocillin 4 g (as the sodium salt) as a 20-minute infusion every six hours for five doses. After a one-week washout period, subjects received identical treatment with the alternate drug. Serum and urine concentrations of piperacillin and azlocillin were measured using a reversed-phase high-performance liquid chromatographic assay, and the pharmacokinetic analysis of serum concentration-versus-time data was performed using a computerized program. A standard open-model equation for i.v. infusions was used. Mean serum concentrations of piperacillin and azlocillin after dose 5 were 344 +/- 66 micrograms/mL and 414 +/- 86 micrograms/mL, respectively. The terminal elimination half-life of azlocillin (1.1 +/- 0.2 hr) was significantly longer than that of piperacillin (0.75 +/- 0.13 hr) (p less than 0.05). Total body clearance of azlocillin (125 +/- 25 mL/min) was significantly less than that of piperacillin (226 +/- 43 mL/min) after dose 5. Azlocillin showed accumulation between the first and fifth doses. Twelve hours after administration of dose 5, 75% of azlocillin and 57% of piperacillin were excreted unchanged into the urine. In healthy volunteers, azlocillin produced higher and more prolonged serum concentrations than piperacillin after administration of equivalent i.v. doses. Further studies are needed to determine the clinical importance of these observations.
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