Tuesday, 30 July
Q2 Solutions Exhibitor Showcase

 

ADME Services to Enable Informed Decision Making in Drug Discovery & Development

Speaker: J. Matthew Hutzler

Time: 16:00 - 16:30

Educational Needs Statement: Educate the audience about the ADME services that Q2 Solutions has, as well as to present novel solutions to deal with complex issues.

Learning Objectives:

  • ADME Services

  • In vitro screening

  • Novel In vitro models

  • Plasticizer impact on plasma fraction unbound

Who Should Attend?

  • Pharmaceutical industry scientists

  • Medicinal chemists

  • DMPK experts

  • Students

Abstract:

Q2 Solutions provides services designed to help clients acquire ADME data needed to drive decisions for pharmaceutical drug candidates in drug discovery and development. Our integrated drug metabolism and pharmacokinetic solutions include high-throughput automated in vitro screening assays, discovery-level and regulated LC-MS/MS bioanalysis, metabolite profiling, and drug-drug interaction (DDI) risk assessments to support clinical pharmacology strategies. Q2 Solutions provides these services as individual offerings or bundled services to support discovery and IND-enabling packages, and also provide novel solutions to overcome especially difficult challenges. In this presentation, two case studies will be presented, including metabolite profiling of low-turnover drugs and addressing factors confounding accurate human plasma protein binding data. Case Study 1: To provide a potential solution for profiling low-turnover drugs, the HuREL® human hepatocyte coculture model was evaluated and results were recently published (Drug Metab Dispos 46(11) 2018). Metabolites of four drugs possessing diverse metabolic pathways (timolol, meloxicam, linezolid, and XK469) were compared following incubations in both suspended cryopreserved human hepatocytes and the HuREL® hepatocyte coculture model. In general, minimal metabolism was observed following 4-hour incubations in suspended hepatocytes, whereas incubations conducted in the HuREL® coculture model resulted in more robust metabolic turnover, with continuous metabolite production observed for up to 7 days of incubation, covering cytochrome P450, aldehyde oxidase, and UGT-mediated pathways. The predominant metabolites correlated well with the most abundant metabolites reported in human clinical studies.