Pharmacokinetic study of piperacillin in newborns relating to gestational and postnatal age

The pharmacokinetics of piperacillin after a single 75-mg/kg intravenous injection as analyzed in 28 neonates with gestational ages of 29 to 40 weeks (A = 29 to 31 weeks, B = 33 to 35 weeks, C = 38 to 42 weeks) and birth weights of 860 to 3900 g during 35 courses. Serum concentrations of piperacillin were determined by high pressure liquid chromatography. A one compartment open model characterized the disposition of piperacillin. Twenty courses were given between Day 3 and Day 5 of life. The elimination half-life and total body clearance were related to gestational age. Differences were significant between Groups A and B and Group C for half-life (4.3 ± 1.9 and 3.35 ± 0.75 vs. 2.47 ± 0.72 hours) and for clearance (1.68 ± 0.6 and 1.8 ± 0.4 vs. 2.46 ± 0.36 ml/min/kg). Volumes of distribution were similar in the 3 groups, from 516 ± 108 to 633 ± 226 ml/kg. Fourteen courses were given from Day 9 to Day 11 of life. The same differences were observed between Groups A and B and Group C. Elimination half-life was significantly reduced with simultaneous increase of the total body clearance. In clinical practice, 75-mg/kg intravenous injections every 12 hours during the first week of life and every 8 hours in the second week provide appropriate concentrations in infants of less than 36 weeks gestational age. In full term newborns the 75-mg dosage is appropriate but the number of injections must be increased to 3/24 h for the first week and 4 times daily there-after.