Ontogeny of midazolam glucuronidation in preterm infants

Purpose: In preterm infants, the biotransformation of midazolam (M) to 1-OH-midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam glucuronide (OHMG) is also decreased. The aim of our study was to investigate the urinary excretion of midazolam and its metabolites OHM and OHMG in preterm neonates following the intravenous (IV) or oral (PO) administration of a single M dose. Methods: Preterm infants (post-natal age 3-13 days, gestational age 26-34 4/7 weeks) scheduled to undergo a stressful procedure received a 30-min IV infusion (n=15) or a PO bolus dose (n=7) of 0.1 mg/kg midazolam. The percentage of midazolam dose excreted in the urine as M, OHM and OHMG up to 6 h post-dose was determined. Results: The median percentage of the midazolam dose excreted as M, OHM and OHMG in the urine during the 6-h interval after the IV infusion was 0.44% (range 0.02-1.39%), 0.04% (0.01-0.13%) and 1.57% (0.36-7.7%), respectively. After administration of the PO bolus dose, the median percentage of M, OHM and OHMG excreted in the urine was 0.11% (0.02-0.59%), 0.02% (0.00-0.10%) and 1.69% (0.58-7.31%), respectively. The proportion of the IV midazolam dose excreted as OHMG increased significantly with postconceptional age (r=0.73, p <0.05). Conclusion: The glucuronidation of OHM appears immature in preterm infants less than 2 weeks of age. The observed increase in urinary excretion of OHMG with postconceptional age likely reflects the combined maturation of glucuronidation and renal function

Efficient uncertainty propagation of lognormal hydraulic conductivity in a three dimensional hydrogeological model of flow and transport on very large regular grids

Proceedings of IAMG 2015 - 17th Annual Conference of the International Association for Mathematical Geosciences 2015, Pages 369-377This work illustrates an efficient method for Monte Carlo uncertainty analysis in a three dimensional hydrogeological context involving very large grids. Although Monte Carlo simulation using Simple Random (SR) sampling is the de facto method for such an uncertainty analysis, it quickly becomes expensive in terms of time and computer resources, particularly for the case of complex models. To alleviate this problem, a new Latin Hypercube (LH) sampling method is proposed in this work for efficiently generating realizations of secondorder stationary lognormal random fields on large (order of million pixels) regular grids. he performance of the proposed LH sampling method is compared to that of SR sampling in the context of a 3D hydrogeological flow and transport model. The results show that the proposed LH sampling is more efficient than SR sampling, in that it can overall reproduce to a similar extent statistics of the conductivity (and associated concentration) field, yet with smaller sampling variability than the latter

DECONVOLUTION OF OVERLAPPING HPLC AROMATIC HYDROCARBONS PEAKS USING INDEPENDENT COMPONENT ANALYSIS (ICA)

Chemometric methods like Principal Component Analysis (PCA) and Evolving Factor Analysis (EFA) have been applied to improve peaks separation, especially in HPLC UV-DAD analysis. In this work, the Independent Component Analysis (ICA) was adopted for the separation of overlapping aromatic peaks and the simultaneous determination of the underlying spectra. The application of the method on middle petroleum fraactions showed an improved separation between the aromatic groups compared to the previously used methods. The determined by the ICA method UV spectra of the component groups can be further exploited for the compositional characterization of the aromatic fractions. CC 200