ABSTRACT
Information of metabolic enzymes and transporters, physiological parameters of animals and demography of Chinese people were integrated to establish a digital liver model (DLM) based on metabolism and transporter and coded with VBA. Clearance and drug-drug interaction (DDI) of candidate drugs in animal and human could be predicted based on the pharmacokinetic data obtained from in vitro and in vivo experiments. Pravastatin and pitavastatin were selected as the samples to examine this model, where their clearance and their DDI with cyclosporine were predicted. The results showed that the predicted values of median parameters in same species were within twofold of observed values for 83.3% (5/6). The program's successful prediction in DDI tendency might indicate its application in optimizing the dosage regimen and reducing the risk of clinical trial.
Subject(s)
Cyclosporine/pharmacokinetics , Liver/metabolism , Models, Biological , Pravastatin/pharmacokinetics , Quinolines/pharmacokinetics , Animals , Area Under Curve , Biological Transport , Computer Simulation , Drug Interactions , Humans , Metabolic Clearance Rate , Pravastatin/blood , Quinolines/bloodABSTRACT
Glutathione is a tripeptide comprised by L-glutamate, L-cysteine, and glycine, that serves antioxygenation and deintoxication functions within the cell. Recent study has found that glutathione is the main driving force for bile salt-independent bile flow, impaired biliary excretion of glutathione can lead to cholestasis. This review focuses on hepatobiliary transport of glutathione and its role in cholestasis. Based on the evidence of choleretic effect of glutathione, enhancement of biliary excretion of glutathione may be a good strategy for prevention and treatment of cholestasis.
Subject(s)
Cholestasis/prevention & control , Glutathione/metabolism , Jaundice, Chronic Idiopathic/genetics , Liver/metabolism , Multidrug Resistance-Associated Proteins/metabolism , Animals , Biological Transport , Cholestasis/chemically induced , Cholestasis/metabolism , Estrogens/adverse effects , Humans , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics , Mutation , Phalloidine/adverse effects , Ursodeoxycholic Acid/therapeutic useABSTRACT
The speech delivered by Mrs. Sanger at the Peking University in April, 1922 marked the pushing forward of public movement of modern birth control in the society. An institution was set up, special magazines and works published in that year. In 1930, the establishment of Peiping Health Society for Women and Children, the first of its kind in China, marked the practical stage of instruction and public education on the works of birth control.
