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Cefazolin (CFZ) is highly and saturably bound to human serum albumin (HSA) in adults. We aim to describe CFZ protein binding and its covariates in neonates. In neonates to whom intravenous CFZ (50 mg/kg) was administered prior to a surgical procedure, total and unbound CFZ plasma concentrations (mg/l) were determined at 0.5, 2, 4 and 8 h after CFZ administration. Linear and multiple regression analyses were used to document covariates of unbound CFZ fraction. The Wilcoxon signed-rank test was used for the paired analysis of unbound CFZ fractions. In 40 patients with a median weight of 2,767 (range 830-4,200) g and a postmenstrual age (PMA) of 39 (25-45) weeks, 131 samples were collected. The median unbound CFZ fraction was 0.39 (0.10-0.73). Linear regression of unbound CFZ fraction versus unbound CFZ plasma concentration ( R = 0.39) had a slope significantly different from zero ( p < 0.001). In a multiple regression analysis, albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA resulted in an R value of 0.496. The median unbound CFZ fraction at the peak concentration (0.46, range 0.28-0.69) was significantly higher compared to the trough level (0.36, range 0.17-0.73) ( p < 0.001). The between- and within-patient saturability of CFZ plasma protein binding were documented in neonates. The median unbound CFZ fraction in neonates is higher than in adults and depends partly on albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA. Integration of CFZ protein binding in future pharmacokinetic/pharmacodynamic research is warranted in order to optimise neonatal CFZ dosing. We recommend protein binding assessment in the neonatal pharmacokinetic evaluation of highly protein-bound or clinically relevant drugs. [ABSTRACT FROM AUTHOR]

The article presents a study which measures voriconazole plasma levels in children. The study conducted voriconazole plasma concentration monitoring, C-reactive protein levels (CRP), liver function tests, renal function tests, serum galactomannan (GM) values in patients, aged 0-18 years, admitted in a tertiary care hospital in Leuven, Belgium. Results show that voriconazole levels varied widely and no correlation were observed between trough levels and administered dosage.

Objective: Assess in vivo O-demethylation activity in the first months of life. Methods: Time-concentration profiles of tramadol (M) and O-demethyl tramadol (M1) in plasma and urine were simultaneously collected in the first 24 h of continuous intravenous tramadol administration in neonates and young infants. M and M1 were determined by high performance liquid chromatography. Correlations between perinatal characteristics [postnatal age (PNA), postmenstrual age (PMA)] and the contribution of metabolites (M, M1) to overall tramadol elimination and to the plasma and urine log M/M1 were calculated. Results: Plasma samples were available in 20/29 and complete complete 24-h urine collections were available in 25/29 neonates (25–53 weeks PMA). Mean plasma log M/M1 value (»4 h, n=86) was 0.8 (SD 0.4). A significant correlation between plasma log M/M1 and PMA (r=-0.73, P«0.0001) and PNA (r=-0.58, P«0.005) was observed. In a multiple regression model, only PMA remained an independent variable. Mean urine log M/M1 was 0.94 (SD 0.7). Significant correlations of the urine log M/M1 ratio with PMA (r=-0.73, P«0.0001) and PNA (r=-0.56, P=0.0035) were observed. In a multiple regression model with the urine log M/M1ratio as dependent variable, only PMA remained an independent variable. The maturational half-life of the log M/M1 ratio in early neonatal life in the age range evaluated is about 12–16 weeks without plateau. Conclusions: O-demethylation activity was already observed in early neonatal life. A significant correlation with PMA was documented, but PMA can only partially explain the observed variability in O-demethylation activity. Polymorphism therefore likely already contributes to the interindividual variability observed in neonates. [ABSTRACT FROM AUTHOR]