Abstract
In order to optimize the dosage regimen of vancomycin in neonates, we investigated the population pharmacokinetics and the influence of covariates on the individual pharmacokinetic parameters. Data from 105 preterm and term neonates were analyzed retrospectively. Their Post Conceptional Age (PCA) ranged from 26.5 to 44.1 weeks. Post Natal Age (PNA) was 13.7 (8.2) (mean (s.d.), range: 4–54 days. Plasma vancomycin trough and peak concentration pairs were routinely obtained around the second dose and on several days thereafter (mean 5.8 concentrations/infant). Routine gentamicin drug monitoring, immediately preceding the vancomycin course, was available in 65 infants (mean 4 concentrations/infant). Both population and individual pharmacokinetic parameters of vancomycin were calculated according to a one-compartment open model with a non-parametric expectation maximization algorithm (NPEM2, USCPACK 10.7; University SC, USA). Calculations were also performed with an iterative Bayesian fitting procedure and maximum a posteriori Bayesian fitting (MW\PHARM 3.50, Mediware, The Netherlands). The influence of several demographic and clinical covariates was calculated using stepwise multiple regression analysis with SPSS 10.0 software (Chicago, IL, USA). Recent literature indicates that serum creatinine in the first 2 weeks of life does not reflect glomerular filtration rate [1]. Therefore we also calculated the correlation between Kel gentamicin and Kel vancomycin. Three subgroups were defined: < 30, ≥ 30 and < 37, and ≥ 37 weeks’ PCA. Their population parameters (median + mean DF50+DF95) are reported in the same order: Kel (h−1): 0.0889 (0.0229), 0.1090 (0.0249), 0.1634 (0.0458) and V/W (lkg−1): 0.5487 (0.1362), 0.4950 (0.1368), 0.4229 (0.0914). Results obtained with NPEM2 and MW/PHARM were almost identical. A significant (P < 0.001) correlation was found between Kel of gentamicin and vancomycin (r = 0.579) and between serum creatinine and Kel of vancomycin (r = −0.563). Stepwise multiple linear regression analysis yielded the following statistically significant equations: A significant correlation was demonstrated between vancomycin elimination rate and serum creatinine concentrations. The correlation with gentamicin kinetics could be used in practice if plasma creatinine concentrations are not available or biased. The predictive value of the observed correlations has to be validated prospectively in clinical practice.
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