hupo2017@conferencepartners.ie

Per Artursson

Per Artursson

Talk Title: Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes in the human liver – impact on pharmacokinetic and toxicokinetic predictions

email: per.artursson@farmaci.uu.se

Bio:

Per Artursson is a professor in Dosage Form Design at the Department of Pharmacy, Uppsala University, Sweden where he heads the Drug Delivery research team. He is also Director for the Uppsala University drug optimization and pharmaceutical profiling platform within Science for Life Laboratories. His research aims at understanding drug absorption, distribution, metabolism and elimination (ADME) at the molecular and cellular level in order to deliver drugs more effectively via the oral route. He also investigates the effects of drug transporting proteins on drug disposition and drug interactions. He has published over 200 research articles and reviews, is highly cited and has received several international awards for his research.

Abstract:

Variability in mass spectrometry-based quantification of clinically relevant drug transporters and drug metabolizing enzymes in the human liver – impact on pharmacokinetic and toxicokinetic predictions
Per Artursson, Dept of Pharmacy, Uppsala University
Many different methods are used for mass-spectrometry based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically relevant drug transporters and metabolizing enzymes in human liver. Protein quantities obtained from label-free and targeted methods using whole tissue lysates were in general in good agreement. Methods using subcellular membrane fractionation gave incomplete enrichment of targeted proteins. When these quantified proteins were adjusted to levels in whole tissue lysates, they were on average four-fold lower than those quantified directly in whole tissue lysates. These differences were propagated into differences in pharmacokinetic predictions of hepatic drug clearance in man. In conclusion, caution is needed when applying quantitative proteomics data obtained with different methods in pharmacokinetic and toxicokinetic modeling.