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Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine
C W Kildoo1, L M Lin, M H Gabriel
1Department of Pharmacy, Miller Children's Hospital, Memorial Medical Center, Long Beach, Calif.
Insights
This study on vancomycin pharmacokinetics in preterm infants found that serum creatinine levels, alongside postconceptional age (PCA), are crucial for determining appropriate vancomycin dosing regimens in neonates.
Area of Science:
- Neonatal Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Staphylococcus epidermidis infections are common in preterm infants.
- Vancomycin is a critical antibiotic for treating these infections.
- Optimizing vancomycin dosing in neonates is essential due to their unique pharmacokinetic profiles.
Purpose of the Study:
- To investigate the multidose pharmacokinetics of vancomycin in preterm infants.
- To identify key factors influencing vancomycin clearance and distribution in this population.
Main Methods:
- Studied 15 infants with gestational age < 36 weeks and suspected S. epidermidis infections.
- Administered vancomycin doses (6.7–10.6 mg/kg) over 60 minutes.
- Analyzed pharmacokinetic parameters using a two-compartment model and nonlinear regression.
Main Results:
- Mean vancomycin clearance (CL) was 1.07 ml/min/kg and volume of distribution (Vdss) was 0.48 liters/kg.
- CL was strongly inversely correlated with serum creatinine (r = -0.82).
- CL showed a weaker but significant positive association with postconceptional age (PCA) (r = 0.41).
Conclusions:
- Serum creatinine is a significant predictor of vancomycin clearance in sick preterm infants.
- PCA also influences vancomycin pharmacokinetics.
- Consideration of both serum creatinine and PCA is recommended for initial vancomycin dosing in neonates.
Abstract:
Multidose pharmacokinetics of vancomycin were studied in 15 infants with gestational age less than 36 weeks and suspected or confirmed Staphylococcus epidermidis infections. Postconceptional age (PCA) at the time of the study ranged from 26 to 44 weeks. Vancomycin individual doses ranged from 6.7 to 10.6 mg/kg and were infused over 60 min. Five postinfusion samples were obtained in 13 infants, while 4 samples were obtained in 2 patients. Vancomycin pharmacokinetic parameters were determined by fitting the data to a two-compartment model using a weighted least-squares nonlinear regression method. Mean vancomycin body clearance (CL), volume of distribution (Vdss) and terminal elimination half-life were 1.37 ml/min, 0.58 liters and 5.6 h, respectively. When standardized for patient weight, the CL and Vdss values were 1.07 ml/min/kg and 0.48 liters/kg, respectively. The CL (ml/min/kg) was strongly inversely correlated with the serum creatinine (r = -0.82), while a weaker but significant association was noted with PCA (r = 0.41). These data suggest that in sick infants, in addition to the PCA, serum creatinine should be considered when determining the initial vancomycin dosing regimen.