Clinical pharmacology of extended-spectrum penicillins in infants and children

Abstract

Compared with previously available penicillins, piperacillin, azlocillin, and mezlocillin have increased activity in vitro against gram-negative bacilli. After intravenous administration of conventional doses (50 to 100 mg/kg) in children, peak concentrations of these drugs are approximately 70 to 350 micrograms/ml. For piperacillin, azlocillin, and mezlocillin, the half-lives during the beta elimination phase (t 1/2 beta) are approximately 0.5 to 0.75, 0.8 to 1.7, and 0.8 to 1.0 hours, respectively. In patients receiving the higher dosage, particularly of azlocillin, the t 1/2 beta may be prolonged by approximately 20%. A total daily dosage of 300 mg/kg or 9 gm/m2 given in four to six divided dosages should produce peak concentrations of approximately 150 micrograms/ml, and concentrations greater than 16 micrograms/ml for at least 2 hours after each administration. Lower daily dosages are needed in neonates, but precise dosage recommendations cannot be made at this time. Only approximately 60% of piperacillin and approximately 45% of azlocillin are eliminated unchanged in the urine; thus only modest dosage reductions are needed in patients with decreased renal function. In children, adverse effects have been infrequent.