Developmental pharmacokinetics of mezlocillin in newborn infants.
Single-dose pharmacokinetics of mezlocillin were studied in 53 newborn infants (72% less than or equal to 36 weeks' gestation) given ampicillin and an aminoglycoside for suspected or proved sepsis. Mezlocillin (75 mg/kg IV or IM) 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.
D000328:Adult; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy / Q000378:metabolism; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008802:Mezlocillin / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D008802:Mezlocillin