0000000000054809
AUTHOR
Yoshiyuki Shirasaka
Quantitation of talinolol in rat plasma by LC-MS-MS.
The aim of this study was to develop and validate an assay based on liquid chromatography-tandem mass spectrometry to quantitate talinolol in rat plasma. After a simple protein precipitation step, separation was performed by reversed-phase liquid chromatography using gradient elution with acetonitrile-water-formic acid. Electrospray ionization in the positive ion mode with multiple reaction monitoring was used to analyze talinolol employing propranolol as internal standard. The calibration curve for talinolol was linear over the concentration range 1-250 ng/mL with a correlation coefficient0.995. The method was sensitive (limit of quantitation, 1 ng/mL) and had acceptable accuracy (85-115% …
Quantitative analysis of the effect of controlled-release formulation on nonlinear gastrointestinal absorption of P-glycoprotein substrate talinolol using physiologically based pharmacokinetic absorption model
Abstract Oral absorption of talinolol, a substrate of P-glycoprotein (P-gp), from a sustained-release (SR) formulation was reportedly decreased compared to that from an immediate-release (IR) formulation. The aim of this study was to predict and understand the effect of controlled-release formulation on the oral absorption of P-gp substrates by developing a physiologically based pharmacokinetic (PBPK) absorption model incorporating multiple kinetic parameters obtained from in vitro studies, using talinolol as a model substrate. Simulation analysis using the developed PBPK absorption model indicated that the clinically observed marked decrease in the plasma concentration of talinolol adminis…
Induction of Human P-Glycoprotein in Caco-2 cells: Development of a Highly Sensitive Assay System for P-Glycoprotein-Mediated Drug Transport
The aim of this work is to develop a highly sensitive assay system for P-gp-mediated transport by using two methods, induction of P-gp and short-term culture of Caco-2 cells. To induce P-gp in Caco-2 cells, cells were cultured in vinblastine-containing medium. The mRNA level of P-gp was approximately 7-fold higher in Caco-2 cells cultured with vinblastine (P-gp-induced Caco-2 cells) than in control cells. Western blot analysis showed a significant increase in P-gp expression. After cell differentiation, the mRNA level of P-gp was downregulated, however, P-gp-induced Caco-2 cells still possessed a 5.6-fold higher mRNA level of P-gp compared to control cells. Polarized transport of substrate …