Pharmacy and Pharmaceutical Sciences Commons^™

Quantitative Analysis Of 5-Chloro-2-Methoxy-N-[2-(4-Sulfamoylphenyl)Ethyl]Benzamide (Glyburide Analogue, Ga) In Mouse Plasma And Whole Blood Using A Micro-Extraction And Liquid Chromatography-Tandem Mass Spectrometry, Ankit Zalavadia

Theses and Dissertations

Pharmacokinetic evaluation of 5-chloro-2-methoxy-N-[2-(4- sulfamoylphenyl)ethyl]benzamide in mouse plasma demanded for a suitable bioanalytical method. No reported bioanalytical method exists to-date that can quantify concentration of this compound in any biological matrix. The purpose of this study was 1) to develop and validate a new bioanalytical method using a micro-extraction and LC-MS/MS to quantify the target analyte in mouse plasma and 2) to partially validate the method in whole blood. A bioanalytical method was developed and validated in both matrices for a linear concentration range of 2-1000 ng/ml. For both matrices, the reverse predicted concentration of calibration standards (-8.95% to 12.16% …

Using Semiphysiologically-Based Pharmacokinetic (Semi-Pbpk) Modeling To Explore The Impact Of Differences Between The Intravenous (Iv) And Oral (Po) Route Of Administration On The Magnitude And Time Course Of Cyp3a-Mediated Metabolic Drug-Drug Interactions (Ddi) Using Midazolam (Mdz) As Prototypical Substrate And Fluconazole (Flz) And Erythromycin (Ery) As Prototypical Inhibitors, Mengyao Li

Theses and Dissertations

The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI.

Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on hepatic and gut wall (GW) CYP3A metabolism of MDZ, using available in-vitro/in-vivo information. Model-simulated MDZ …