Dose dependence of piperacillin pharmacokinetics

Pharmacokinetics were evaluated for piperacillin given as doses of 15, 30 and 60 mg/kg body weight to 12 healthy volunteers subdivided into three groups which were each given different dosage levels. For the 15, 30 and 60 mg/kg doses, the serum half-lives were 0.8, 1.0 and 0.9 h, and the disposition phase distribution volume coefficients, delta d. beta, 0.31, 0.30, ad 0.25 l/kg. The total body clearances for the three doses normalized to 70 kg body weight were 18.53, 14.00 and 13.53 l/h for the 15, 30 and 60 mg/kg doses, respectively. The corresponding values for the total area under the curves per 1.0 g dose were 57.1, 75.0 and 79.6 micrograms/ml. The urinary elimination of the antibiotic corresponding to the antimicrobial activity of unchanged drug rose from 50.0 to 71.3% of the dose, for a dose increment of 15 to 60 mg/kg. These results document that piperacillin is subject to dose-dependent pharmacokinetics. Capacity-limited kinetics is a property shared by other ureidopenicillins.