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Cefoperazone pharmacokinetics in preterm infants
Insights
Cefoperazone pharmacokinetics in preterm infants show a prolonged half-life. A 50 mg/kg dose every 12 hours is recommended for effective neonatal infection treatment.
Area of Science:
- Neonatal pharmacology
- Antibiotic pharmacokinetics
- Clinical pharmacy
Background:
- Cefoperazone is a new cephalosporin antibiotic.
- Understanding its pharmacokinetic profile in preterm infants is crucial for safe and effective dosing.
Purpose of the Study:
- To determine the elimination pharmacokinetics of cefoperazone in preterm infants.
- To establish optimal dosing regimens for cefoperazone in this population.
Main Methods:
- Studied 15 preterm infants (32-36 weeks gestational age).
- Administered single intravenous doses of 50 or 250 mg/kg cefoperazone.
- Collected blood samples for drug assay and analyzed pharmacokinetic parameters using noncompartmental analysis.
Main Results:
- Mean plasma half-life was approximately 5.5-5.8 hours.
- Total body clearance was around 35-36 ml/h/kg.
- Positive correlation observed between gestational age and clearance/elimination rate.
- A 50 mg/kg dose every 12 hours achieved adequate serum levels against common neonatal pathogens.
Conclusions:
- Cefoperazone exhibits prolonged elimination in preterm infants.
- Dosing every 12 hours with 50 mg/kg is suggested for effective treatment.
- The drug was well-tolerated with no significant adverse effects noted.
Abstract:
The elimination pharmacokinetics of cefoperazone, a new cephalosporin, were studied in 15 preterm infants ranging in gestational age from 32 to 36 weeks and in postnatal age from 1 to 6 days. The infants received a single dose of either 50 or 250 mg of cefoperazone per kg by intravenous infusion. Blood samples were collected at specified times after completion of the drug infusion and then assayed for cefoperazone. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for plasma half-life, elimination rate constant, apparent steady-state volume of distribution, and total body clearance were 5.53 h, 0.15 h-1, 124 ml/kg, and 36 ml/h per kg, respectively, for the group receiving a 50-mg/kg dose and 5.76 h, 0.14 h-1, 111 ml/kg, and 35 ml/h per kg, respectively, for the group receiving a 250-mg/kg dose. Positive correlations between gestational age and clearance and elimination rate were detected. A 50-mg/kg dose every 12 h ensured adequate serum levels for most of the common neonatal pathogens. Other than a transient rise in eosinophils in four subjects, no adverse effects were noted.