Dosing recommendations for vancomycin, which has primarily renal elimination, are derived from studies demonstrating that renal function in the human neonate increases significantly at approximately 34 wks postconceptional age(PCA, where PCA = gestational age[GA] + PNA). To examine the independent role of PNA, we calculated vancomycin pharmacokinetics (104 studies) in 79 critically-ill neonates. Elimination rate constant (Kel) and volume of distribution (Vd) were determined. As shown in the Table(mean±SD), infants were divided into three GA groups: ≤30, 31-35, and >35 wks(PCA 31.3±3.2, 35.9±3.9, and 42.8±2.0 wks, respectively). Although Kel was greater in the more mature infants, a significant correlation between PNA and Kel was observed within each gestational age group. Furthermore, for all infants with PCA 29-36 wks, the correlation between PNA and Kel was r=.49, p<.0001, N=67;for PCA 29-34 wks, r=.39, p<.01, N=57. In infants with PCA ≤36 wks there was a significant difference in Kel when PNA was <2.5 wks vs ≥2.5wks (.104±.030 vs.131±.040, p=.0009). A significant difference in Kel also was observed in infants with PCA ≤34 wks and PNA <2.5 wks vs ≥2.5 wks(.101±.031 vs.122±.033, p=.009). Differences in Vd in these groups were not observed. While PCA is an important consideration in determining optimal dosing for vancomycin, our results suggest that PNA is an important independent variable which also must be considered. (*p=.018 comparing ≤30 wks with >35 wks)

Table 1
Full size table