Drug Transporters in ADME
Pharmaceutical companies are investing research time into understanding and modelling of drug transporters to better predict drug-drug interactions and toxicities. Whilst understanding drug-drug interactions can enhance study efficiency and drug efficacy, the challenges presented by drug transporters are complex.
Releasing guidance on the subject of drug interaction and transporters in 2010, the European Medicines Agency noted despite much research into the different polymorphisms in drugs transports and their effect on safety, "in the majority of cases the influence of transporter polymorphism on drug pharmacokinetics has not yet been clarified".
It added that currently a number of lead proteins being developed use transporters where the effect of genetic variations is not yet known and these are both factors which are expected to have an impact on future drug discovery.
Along with toxicity, unsatisfactory absorption, distribution, metabolism and excretion (ADME) are some of the key reasons why drugs fail to make it through clinical trials.
Predicting ADME would represent a significant step forward in cutting drug delivery times and boosting safety and efficacy, and this is the aim of a new partnership between Optivia Biotechnology and the University of California, San Fransisco.
The pair were recently granted a $430,000 Phase I grant from the National Institutes of Health for studying how transporter proteins affect the disposition of drugs in the liver and how transporters and metabolising enzymes interact in the organ.
Dr. Yong Huang, president and chief executive officer of Optivia Biotechnology, noted the effect of drug transporters is likely to become an increasingly important part of ADME assessments and are predicted to be the subject of further regulations for new drug applications.
"The industry has long observed discrepancies between measuring drug metabolism in existing experimental system. Transporters likely contribute to the observed discrepancies," he noted.
The eventual aim of the study is to develop a transporter based assay system which will allow for the prediction of ADME in drug candidates.
Phase I of the study sees 40 marketed drugs tested against ten major hepatic transporters, before the information on in vitro drug-transporter interaction and in vivo information on the disposition of drugs in the liver is correlated.