Pharmacology Core

Rhode Island Hospital, Providence RI

Investigators

Abstract

PROJECT SUMMARY Infectious diseases present major health challenges with millions of people affected yearly, demonstrating the need for advancing and optimizing development and dosing strategies for therapeutics. Pharmacokinetics (PK) involves a drug's absorption, distribution, metabolism, and elimination (ADME) processes, influencing key parameters like absorption efficiency, bioavailability, and elimination half-life. Understanding these key PK processes is essential for developing new drugs and optimizing drug dosing for infectious diseases. Hence, we propose a Pharmacology Core (PC) at the University of Rhode Island's College of Pharmacy to support the pharmaceutical projects of the COBRE program "Translational Approaches for Pathogens of Human Significance." The PC will specialize in assessing, analyzing, and modeling PK data to derive essential parameters for drug development and dosing strategies. Its primary objectives include analyzing drug exposures, employing advanced chemical analytics, and establishing in vitro cell-based assays to measure PK parameters for new drug candidates. The PC's scientific approaches aim to facilitate and advance drug candidate screening and dosing strategies for infectious disease treatments. The PC will aid in investigating the incorporation of disease biomarkers in PK models to provide individualized dosing recommendations based on disease progressing, aiming to move beyond generic treatment guidelines. Advancing current PK modeling approaches for drugs for infectious diseases, the pathogen will be incorporated as an additional compartment in PK models to assess the specificity of drug candidates. These novel approaches have the potential to serve as proof-of-concept studies and could be applied in future PK studies to optimize development and dosing of drugs for infectious diseases. A long-term objective of the PC is to provide comprehensive training in Pharmacology, specifically PK modeling, to the RPLs the Pathogens COBRE team. Training components will cover basic PK models (including underlying mathematics and codes), derivation of model parameters using in vitro cell assays, and chemical analytics. Trainees will learn how to derive essential PK parameters (e.g., elimination half-life, volume of distribution) from plasma concentration profiles measured in animal or human Cohort studies. These acquired skills pave the way for RPLs to incorporate PK research components into future grant applications post-COBRE. The PC is led by Dr. Slitt, a toxicologist and drug disposition expert with over 25 years of experience, overseeing drug analytics, data interpretation, manuscript preparation, and reporting. Dr. Fischer, the Co-Director, applies his PK expertise to enhance drug development and dosing strategies for infectious diseases, involving comprehensive PK assessments, modeling, and the establishment of in vitro PK assays. Dr. Achour specializes in PK within special and disease populations, will contribute significantly to assessing and modeling PK data generated within the COBRE projects.