Developmental pharmacokinetics of mezlocillin in newborn infants

Single-dose pharmacokinetics of mezlocillin were studied in 53 newborn infants (72%≤36 weeks' gestation) given ampicillin and an aminoglycoside for suspected or proved sepsis. Mezlocillin (75 mg/kg IV or 1M) was substituted for ampicillin, serum was assayed microbiologically, and noncompartmental pharmacokinetic parameters were calculated. Analysis of covariance showed that dose/area under the serum concentration-time curve for mezlocillin was influenced by body weight, intramuscular administration, and treatment with gentamicin. A dual intravenous/intramuscular nonlinear regression model yielded an apparent intramuscular bioavailability of 84%. Clearance was proportional to body weight (WT) (r²=0.70). Mean CL/WT (0.078 L/hr/kg) was one-half adult values and influenced by gestational age. Steady-state volume of distribution varied linearly with weight (r²=0.80), the mean value (0.38 L/kg) being twice that in adults. Mezlocillin half-life (mean 3.71 hours) exceeded adult values and did not correlate with weight. Twenty-four newborn infants received 75 mg/kg mezlocillin every 6 or every 8 hours, along with gentamicin, during the first 7 to 10 days of life. Peak (1.5 hours) and trough (6 or 8 hours) concentrations were determined; the latter decreased from day 3 to days 7 to 10, suggesting a possible postnatal age-dependent change in mezlocillin elimination. Although mezlocillin disposition is affected by age and therapeutic factors, weight alone may adequately predict dosing requirements.