Abstract
Previous studies evaluating aminoglycoside (A) disposition in premature infants have described the relationship between various indices of maturation and serum A clearance as either linear or exponential. Pharmacokinetic studies carried out in 992 infants demonstrated a distinctly bi-phasic pattern when indices of A elimination are compared to indices of maturation. Gestational age (GA) 24-39 wks, postnatal age (PNA) 1-20 wks, postconceptional age (PCA) 25-53 wks, birthweight (BW) 380-3950 gm and study weight (SW) 350-4620 gm were recorded. Serial A serum concentrations were determined by RIA. Volume of distribution (Vd) 0.29-0.63 L/kg, elimination rate constant (Ke) 0.029-0.231 hr-1, and serum clearance (C1) 0.0056-0.630 L/hr were calculated. When Ke and Cl were compared to GA, PCA, BW and SW, the relationship was distinctly bi-phasic. Prior to 34 wks GA and 35 wks PCA, Ke and Cl increased slowly with respect to increased GA and PCA. After 35 wks GA and 36 wks PCA, Ke and Cl increased rapidly with respect to increasing GA and PCA. These changes at 34-36 wks may represent a functional change in the neonatal kidney at this stage of maturation. Vd (L/KG) was found to decrease slightly with increasing GA, PCA, BW and SW. This data suggests that neither a linear nor exponential model fully describes the improvement of A Cl in the neonate. A biphasic model with a breakpoint at 34 wks GA or 35 wks PCA appears to be the most appropriate description of the improvement. Therefore, GA and PCA are important variables to evaluate in the determination of A dosing recommendations.
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Harralson, A., Klldoo, C., Deal, R. et al. DEVELOPMENTAL PATTERN OF AMINOGLYCOSIDE DISPOSITION IN PREMATURE INFANTS: BI-PHASIC CHANGES IN SERUM CLEARANCE. Pediatr Res 21 (Suppl 4), 236 (1987). https://doi.org/10.1203/00006450-198704010-00412
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DOI: https://doi.org/10.1203/00006450-198704010-00412