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Developmental pharmacokinetics of mezlocillin in 4 newborn infants
G L Jungbluth1, F H Wirth, T T Rubio
1Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo.
Insights
Mezlocillin clearance in newborns is lower than in adults but improves with postnatal development. This antibiotic
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Neonates exhibit unique physiological characteristics affecting drug disposition.
- Understanding mezlocillin pharmacokinetics in newborns is crucial for optimizing therapy.
Purpose of the Study:
- To evaluate the disposition of mezlocillin in newborn infants.
- To assess the impact of postnatal development on mezlocillin pharmacokinetics.
Main Methods:
- Sequential two-phase study in 4 neonates at 1 day and 8-10 days postnatal age.
- Measurement of serum concentrations and urinary excretion rates.
- Estimation of renal function using creatinine clearance (CLCR).
Main Results:
- Weight-normalized mezlocillin clearances (total, renal, nonrenal) and CLCR were lower than adult values.
- Clearances and CLCR increased with postnatal development.
- Elimination half-lives were shorter by phase II.
- Both renal and nonrenal elimination enhanced by 1 week of postnatal development.
Conclusions:
- Mezlocillin disposition in neonates is influenced by body weight, gestational age, and postnatal age.
- Postnatal development significantly enhances mezlocillin elimination.
- Pharmacokinetic parameters mature rapidly within the first week of life.
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.