Novel testing strategy for prediction of rat biliary excretion of intravenously administered estradiol-17 beta glucuronide
ARCHIVES OF TOXICOLOGY
Authors: Noorlander, Annelies; Fabian, Eric; van Ravenzwaay, Bennard; Rietjens, Ivonne M. C. M.
Abstract
The aim of the present study was to develop a generic rat physiologically based kinetic (PBK) model that includes a novel testing strategy where active biliary excretion is incorporated using estradiol-17 beta glucuronide (E(2)17 beta G) as the model substance. A major challenge was the definition of the scaling factor for the in vitro to in vivo conversion of the PBK-model parameter V-max. In vitro values for the V-max and K-m for transport of E(2)17 beta G were found in the literature in four different studies based on experiments with primary rat hepatocytes. The required scaling factor was defined based on fitting the PBK model-based predicted values to reported experimental data on E(2)17 beta G blood levels and cumulative biliary E(2)17 beta G excretion. This resulted in a scaling factor of 129 mg protein/g liver. With this scaling factor the PBK model predicted the in vivo data for blood and cumulative biliary E(2)17 beta G levels with on average of less than 1.8-fold deviation. The study provides a proof of principle on how biliary excretion can be included in a generic PBK model using primary hepatocytes to define the kinetic parameters that describe the biliary excretion.
Decisive role of adsorption affinity in antibiotic adsorption on a positively charged MnFe2O4@CAC hybrid
SCIENCE OF THE TOTAL ENVIRONMENT
Authors: Chen, Quan; Yi, Peng; Dong, Wei; Chen, Yihui; He, Liping; Pan, Bo
Abstract
The discharge and consequent occurrence of antibiotics in the environment has led to increasing concerns because their presence can promote the development of resistance genes, which in turn pose a significant health risk. A key process to control the transport and risk of antibiotics is adsorption. Thus, we investigated the adsorption mechanisms of six typical antibiotics onto a MnFe2O4@cellulose activated carbon (CAC) hybrid combining batch adsorption experiments and quantum chemical calculations. In the single-adsorbate adsorption systems, the solid-phase concentrations of the adsorbates varied from 152.8 to 395.7 mg/g, which were dependent on the adsorption affinity and molecular structures or sizes of the antibiotics. Chemisorption was the main adsorption mechanism, and it was driven by p-d electronic conjugation and cation-n interactions. In the competitive adsorption systems, the solid-phase concentrations of both primary (sulfamethazi ne, SMT) and secondary (the other five antibiotics) adsorbates decreased significantly. The decrease ratio of SMT varied from 15.42% to 67.28% while that of the secondary adsorbates varied from 14.13% to 52.74%. The "competition" strength was depended on the adsorption energy and the overlapping of adsorption sites. We believe that these findings will provide a better understanding of the adsorption characteristics of typical antibiotics and facilitate the strategy developing for the removal of antibiotics from the aqueous phase. (C) 2020 Elsevier B.V. All rights reserved.