Predictability of human pharmacokinetics of diisononyl phthalate (DINP) using chimeric mice with humanized liver.

1. In order to investigate the pharmacokinetics of diisononyl phthalate (DINP) in humans, we administered [phenyl-U-C]DINP at a dose of 50.0 mg/kg orally to chimeric mice (humanized-liver mice) in which the liver of TK-NOG mice (control mice) was replaced with human hepatocytes.

Human urinary concentrations of monoisononyl phthalate estimated using physiologically based pharmacokinetic modeling and experimental pharmacokinetics in humanized-liver mice orally administered with diisononyl phthalate.

Diisononyl phthalate (DINP) used as a plasticizer is a mixture of compounds consisting of isononyl esters of phthalic acid. There are concerns about the bioaccumulation of such esters in humans. A [phenyl-U-C]DINP mixture was synthesized and orally administered (50 mg/kg body weight) to control and humanized-liver mice and their pharmacokinetics were determined.

Impact of intestinal glucuronidation on the pharmacokinetics of raloxifene.

Raloxifene is extensively glucuronidated in humans, effectively reducing its oral bioavailability (2%). It was also reported to be glucuronidated in preclinical animals, but its effects on the oral bioavailability have not been fully elucidated. In the present study, raloxifene and its glucuronides in the portal and systemic blood were monitored in Gunn rats deficient in UDP-glucuronosyltransferase (UGT) 1A, Eisai hyperbilirubinemic rats (EHBRs), which hereditarily lack multidrug resistance-associated protein (MRP) 2, and wild-type rats after oral administration.

Structural and ligand-binding properties of serum albumin species interacting with a biomembrane interface.

In the process of drug development, preclinical testing using experimental animals is an important aspect, for verification of the efficacy and safety of a drug. Serum albumin is a major binding protein for endogenous and exogenous ligands and regulates their distribution in various tissues. In this study, the structural and drug-binding properties of albumins on a biomembrane surface were investigated using reverse micelles as a model membrane.

Cooperative effect of hydrophobic and electrostatic forces on alcohol-induced alpha-helix formation of alpha1-acid glycoprotein.

Alpha1-acid glycoprotein (AGP) is a serum glycoprotein that mainly binds basic drugs. Previous reports have shown that AGP converts from a beta-sheet to an alpha-helix upon interaction with biomembranes. In the current studies, we found that alkanols, diols, and halogenols all induce this conformational change.

Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans.

Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of the glycosides of the diterpene derivative steviol. The aims of this study were to investigate the absorption (in rats) and the hepatic metabolism (in rats and humans) of both stevia mixture and steviol. Absorption was investigated both in vivo and ex vivo.

Structural and drug-binding properties of alpha(1)-acid glycoprotein in reverse micelles.

Alpha(1)-acid glycoprotein (AGP) is a glycoprotein that consists of 183 amino acid residues and five carbohydrate chains and binds to neutral and basic drugs. We examined the structural properties and ligand-binding capacity of AGP in interactions with reverse micelles. Also, detailed information was obtained by comparing several different states of AGP.