ABSTRACT
Advanced liver fibrosis and coronary artery calcification (CAC) progression has been reported to correlate with cardiovascular disease. This study investigated the association between noninvasive liver fibrosis score and CAC progression in patients with nonalcoholic fatty liver disease (NAFLD). We included 1173 asymptomatic adults with CAC scores from 2007-2013. CAC progression was defined as newly incident CAC or a ≥ 2.5-unit increase in the final CAC score square root. Liver fibrosis was assessed using fibrosis-4 index (FIB-4) score and NAFLD fibrosis score (NFS). A total of 293 (25.0%) subjects developed CAC. Mean baseline FIB-4 score was significantly higher in subjects with CAC. CAC progressed in 20.5% of subjects without NAFLD, 27.5% of those with NAFLD and low FIB-4 scores, and 35.9% of those with NAFLD and intermediate/high FIB-4 scores. On multivariate logistic regression analysis, the odds ratio for CAC progression was 1.70 (95% confidence interval, 1.12-2.58) for subjects with NAFLD plus intermediate/high FIB-4 scores versus those without NAFLD. In the sensitivity analysis, the odds ratio for CAC progression was 1.57 (95% confidence interval, 1.02-2.44) for subjects with NAFLD plus an intermediate/high NFS versus those without NAFLD. Advanced liver fibrosis stage assessed using noninvasive markers is associated with a higher risk of CAC progression in subjects with NAFLD.
Subject(s)
Coronary Artery Disease/pathology , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/pathology , Vascular Calcification/pathology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/etiology , Disease Progression , Female , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Severity of Illness Index , Vascular Calcification/diagnosis , Vascular Calcification/etiologyABSTRACT
HSG4112, a racemic drug, is a new anti-obesity agent. In this study, the stereoselective pharmacokinetics of HSG4112 were investigated in rats and dogs, and the underlying mechanism was investigated. The plasma concentrations of HSG4112(S) and HSG4112(R) were quantitated in plasma from rats and beagle dogs after IV and/or oral administration of racemic HSG4112. The concentration of HSG4112(S) was significantly higher than that of HSG4112(R) in rat plasma. Contrarily, the concentration of HSG4112(R) was significantly higher than HSG4112(S) in dog plasma. A metabolic stability test with liver microsomes showed that HSG4112(S) was more stable than HSG4112(R) in rat liver microsomes, but the difference between stereoisomers did not appear in dog liver microsomes. However, the stereoselectivity was observed in dog liver and intestinal microsomes after uridine 5'-diphospho-glucuronic acid was added. Thus, stereoselective metabolism by uridine 5'-diphospho-glucuronosyltransferases is mainly responsible for the stereoselective pharmacokinetics in dogs. These results suggest that the species difference in the stereoselective plasma pharmacokinetics of HSG4112 is due to the stereoselective metabolism.
ABSTRACT
Acetyl tributyl citrate (ATBC) is an (the Food and Drug Administration) FDA-approved substance for use as a pharmaceutical excipient. It is used in pharmaceutical coating of solid oral dosage forms such as coated tablets or capsules. However, the information of ATBC on its pharmacokinetics is limited. The aim of this study is to investigate the pharmacokinetic properties of ATBC using liquid chromatographyâ»tandem mass spectrometric (LCâ»MS/MS) analysis. ATBC was rapidly absorbed and eliminated and the bioavailability was 27.4% in rats. The results of metabolic stability tests revealed that metabolic clearance may have accounted for a considerable portion of the total clearance of ATBC. These pharmacokinetic data would be useful in studies investigating the safety and toxicity of ATBC.
