379 PHARMACOKINETICS OF PIPERACILLIN IN INFANTS AND CHILDREN

Abstract

Piperacillin (PIP) is a new penicillin derivative with enhanced activity against gram-negative organisms. We evaluated the pharmacokinetics of this compound in 13 children (ages 1.1-12.7 years). 5 children had Pseudomonas infections (3 osteitis, 1 urinary tract infection, 1 peritonitis). 1 child had foot cellulitis and the remaining 8 had fever and neutropenia. Piperacillin was administered by constant 30 min. intravenous infusion; blood was collected at the end of the infusion and 30, 60, 90 and 120 min. thereafter. The concentration of Piperacillin in serum was determined by a newly developed HPLC assay. The data appeared to fit a one compartment model with first order kinetics. Preliminary results from patients with normal renal function revealed a narrow range of serum half-life(T½); 25.7 to 32.2 min. The apparent volume of distribution (Vd) varied from 0.19 to 0.35 L/Kg. Total body clearance (C1_B) varied from 155 to 361 ml/min/1.73m²; C1_B correlated directly with creatinine clearance (r=.87) In one patient with renal failure (Creat. clear = 6.9 ml/min/1.73m²) the T½ (70.6 min) was prolonged and the C1_B (104 ml/min/1.73m²) was slightly decreased. This suggests that PIP is

eliminated both by renal excretion and by non-renal mechanisms; determinations of urinary excretion and renal clearance of PIP are in progress. These initial data suggest that a desired peak concentration of 150 μg/ml can be achieved with an average dose of 55 mg/Kg; drug accumulation does not occur with dosing intervals of 4 hours in patients with normal renal function.

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