Developmental pharmacokinetics of mezlocillin in 4 newborn infants

Abstract

The disposition of mezlocillin was evaluated in 4 newborn infants in a sequential two-phase study at postnatal ages of 1 day and 8 or 10 days. Renal function was estimated by creatinine clearance (CLCR) and pharmacokinetic parameters of mezlocillin was were determined from serum concentrations and urinary excretion rates. All weight-normalized mezlocillin clearances (total, renal, and nonrenal) and CLCR were less than adult values, but increased after 8 or 10 days of mezlocillin therapy and postnatal development. The volume of distribution at steady state did not significantly change throughout this period, and approximated the expanded extracellular fluid volume typically found in neonates. The elimination half-lives were substantially shorter by phase II of the study. Both renal and nonrenal elimination processes were enhanced by 1 week of postnatal development even though body weight did not increase. Mezlocillin disposition in neonates is thus affected by body weight, gestational age, and postnatal age.