Prediction of drug disposition in diabetic patients by means of a physiologically based pharmacokinetic model.

Background And Objective: Accumulating evidence has shown that diabetes mellitus may affect the pharmacokinetics of some drugs, leading to alteration of pharmacodynamics and/or toxic effects. The aim of this study was to develop a novel physiologically based pharmacokinetic (PBPK) model for predicting drug pharmacokinetics in patients with type 2 diabetes mellitus quantitatively.

Methods: Contributions of diabetes-induced alteration of physiological parameters including gastric emptying rates, intestinal transit time, drug metabolism in liver and kidney functions were incorporated into the model.

Association of GLP-1 secretion with anti-hyperlipidemic effect of ginsenosides in high-fat diet fed rats.

Objective: Ginsenosides, major bioactive constituents in Panax ginseng, have been shown to exert anti-hyperlipidemia effects. However, the underlying mechanism was not well-elucidated due to the low bioavailability of ginsenosides. Glucagon-like peptide-1 (GLP-1) was considered to be a critical regulator of energy homeostasis.

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides.

Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood.

P-glycoprotein and multidrug resistance-associated protein 2 are oppositely altered in brain of rats with thioacetamide-induced acute liver failure.

Background: P-glycoprotein (P-GP) and multidrug resistance-associated protein 2 (MRP2) are involved in transport of many drugs across blood-brain barrier (BBB). The function and expression of P-GP and MRP2 may be modulated by different pathologies. Acute liver failure (ALF) was reported to impair BBB function, resulting in the increased BBB permeability.

Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats.

Aim: To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E(2) (PGE(2)) as a biomarker.

Methods: The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats. PGE(2) level in the rats was measured using an enzyme immunoassay.

Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells.

Aim: To investigate the effects of nitric oxide (NO) donors on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells.

Methods: Caco-2 cells were exposed to NO donors for designated times. P-gp function and expression were assessed using Rhodamine123 uptake assay and Western blotting, respectively.