Renal Function Descriptors in Neonates: Which Creatinine‐Based Equation Best Describes Vancomycin Clearance?

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BACKGROUND: Glomerular function develops rapidly in the first month of life. Several estimated glomerular filtration rate (eGFR) equations have been applied to estimate the rate of clearance (CL) of renally-excreted drugs. This study aimed to compare eGFR with reference values and analyze their influence on vancomycin CL. Data were collected for neonates (3-30 days postnatal age; PNA) with ≥ 1 vancomycin serum concentration(s). Complete data could not be analyzed before September 8, 2014. A population PK model was constructed using NONMEM 7.2. eGFR was calculated using creatinine (Cr)-based equations from modified Schwartz (1), Leger (2), Pottel (3), and British Columbia’s Children’s Hospital (4) equations. Reference eGFR values were derived from Cr. RESULTS: A total of 528 neonates contributed vancomycin 6121 concentrations. The median gestational age (GA) was 29 (IQR 25-36) weeks. Schwartz equation provided comparable results with reference values in preterm neonates, i.e. 24.4 (20.6-26.6) mL/min/1.73 m2 at 14 days PNA in 29 weeks GA infants. In contrast, elevated eGFR were obtained: 46.7+/- 18.2 (2) 52.8 +/- (3), and 44.9 +/-17.6 (4) mL/min/1.7 m2. Theser were close to the values using equations based on cystatin C. Vancomycin PK was analyzed using a one-compartment model with first-order elimination. Weight, postmenstrual age, and eGFR were significant covariated for CL. Between-subject variability decreased by 38.3% with the inclusion of eGRF alone. Although Schwartz equation contributed the best fit, estimated CL (0.13 =/- 0.1 L/hr/kg) across eGRF equations were in reasonable agreement with literature values. Conclusion: Inclusion of eGFR can be used to estimate vancomycin C. The modified Schwartz equation was the best predictor of vancomycin CL in this neonatal population.


Presented at the 116th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics.