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71.
Helene Chapy Sylvie Klieber Priscilla Brun Sabine Gerbal‐Chaloin Xavier Boulenc Olivier Nicolas 《Biopharmaceutics & drug disposition》2015,36(8):491-506
Physiological based pharmacokinetic (PBPK) modeling is now commonly used in drug development to integrate human or animal physiological data in order to predict pharmacokinetic profiles. The aim of this work was to construct and refine a PBPK model of irbesartan taking into account its active uptake via OATP1B1/B3 in order to predict more accurately its pharmacokinetic profile using Simcyp®. The activity and expression of the human hepatocyte transporters OATP1B1 and OATP1B3 were studied. The relative activity factors (RAFs) for OATP1B1 and OATP1B3 transporters were calculated from intrinsic clearances obtained by concentration dependent uptake experiments in human hepatocytes and HEK overexpressing cells: RAF1B1 using estrone‐3‐sulfate and pitavastatine clearances, and RAF1B3 using cholecystokinine octapeptide (CCK‐8) clearances. The relative expression factor (REF) was calculated by comparing immunoblotting of hepatocytes (REFHH) or tissues (REFtissue) with those of overexpressing HEK cells for each transporter. These scaling factors were applied in a PBPK model of irbesartan using the Simcyp® simulator. Pharmacokinetic simulation using REFHH (1.82 for OATP1B1, 8.03 for OATP1B3) as an extrapolation factor was the closest to the human clinical pharmacokinetic profile of irbesartan. These investigations show the importance of integrating the contribution of the active uptake of a drug in the liver to improve PBPK modeling. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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Roseline Porignaux Vincent Vuiblet Coralie Barbe Yohan Nguyen Sylvie Lavaud Olivier Toupance Laurent Andréoletti Philippe Rieu Nicolas Lévêque 《Journal of medical virology》2013,85(6):1115-1121
Described for the first time in 1986, Parvovirus B19 (B19V) infection in kidney transplant recipients remains little‐known and probably underestimated. The aims of this study were to establish B19V infection frequency during the first year after kidney transplant and to determine predisposing factors and manifestations of the infection in renal transplant recipients. Sixty consecutive adult patients, transplanted less than a year before, were included in this study. B19V and other opportunistic viral infections were detected retrospectively in plasma samples collected every 15 days during the first 3 months and every month from 3 months to 1 year following the kidney transplant. Demographic characteristics, immunosuppressive treatment and biological findings were recorded on each sampling date. Six patients (10%) presented B19V viremia, while eight CMV (13.3%), seven EBV (11.7%), five HHV‐6 (8.3%), five BKV (8.3%), and two adenovirus (3.3%) infections were detected. The mean value of B19V viral load was 149 UI/ml. B19V infections were either reactivation or reinfection due to genotype two in five cases, while one case of primary infection with genotype 1 was observed. Neither risk factors nor biological consequences of B19V infection have been identified. These results rank B19V third among opportunistic viral infections occurring during the first year after a kidney transplant. With regard to this high incidence, and even if the risk factors and biological consequences of the infection should be assessed in larger studies, the question of systematic screening and follow‐up of B19V infection in kidney transplant recipients is relevant. J. Med. Virol. 85: 1115–1121, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
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Crutel Véronique Lambert Estelle Penelaud Pierre-François Albarrán Severo Cristina Fuentes Joaquin Rosier Antoine Hervás Amaia Marret Stéphane Oliveira Guiomar Parellada Mara Kyaga Simon Gouttefangeas Sylvie Bertrand Marianne Ravel Denis Falissard Bruno 《Journal of autism and developmental disorders》2021,51(8):2973-2973
Journal of Autism and Developmental Disorders - The author of the article would like to add a video abstract as a supplementary material for a published article. The supplementary file is published... 相似文献
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Aliya Ishmukhametova Jian‐Min Chen Rafaëlle Bernard Bernard de Massy Frédéric Baudat Amandine Boyer Déborah Méchin Delphine Thorel Brigitte Chabrol Marie‐Claire Vincent Mireille Claustres Sylvie Tuffery‐Giraud 《Human mutation》2013,34(8):1080-1084
Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication–triplication rearrangement involving exons 45–60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication‐inverted triplication–duplication (DUP–TRP/INV‐DUP) events; specifically, a 690‐kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46‐kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X–Y chromosome recombination during male meiosis, we proposed an alternative two‐step model for the generation of this X‐linked DMD DUP–TRP/INV‐DUP event. 相似文献