Phenotyping and genotyping at your finger tips

Conventionally, plasma has been used for the determination of exposures and pharmacokinetics (PK) of new chemical entity drugs in clinical trials because of its ease of handling, shipping, and storage compared to whole blood. However, it is notable that regulatory authorities acknowledge that blood is an acceptable biological matrix for the measurement of drug exposures. The collection of blood samples on paper, known as Dried Blood Spots (DBS), is an upcoming technique for use in humans for therapeutic drug monitoring and PK studies. It offers a number of advantages over conventional plasma sampling, i.e. small blood volumes required for DBS samples, the technique being less invasive, more simple preparation and transfer and easy storage and shipment.

Besides blood sampling for PK and phenotyping purposes, DBS has also been reported as sampling and sample storage tool for genotyping. We see a large potential for DBS genotyping in a drug development setting as well, mainly for convenience reasons for subjects, ease of sample shipment and storage and more simple sample preparation procedures with DBS.

Xendo’s scientists and medical experts have strong believe in the future of the DBS technology in Drug Development. A study protocol has been designed to evaluate this technology in Xendo’s Phase I clinical research unit and the bioanalytical laboratories. The study involves pharmacokinetic, pharmacodynamic and pharmacogenetic sampling and bioanalysis using midazolam as model study drug to investigate Cytochrome P450 activity.

The conduct of the IRB approved open-label study in healthy volunteers with 7.5 mg midazolam tablets is in March and has the following objectives:

-          Compare PK results obtained from different sampling techniques (venipuncture collected DBS, whole blood samples and finger prick collected DBS) (midazolam and metabolite) and UHPLC-MS

-          Compare different punching approaches from DBS and evaluate stability of DBS samples

-          Compare DBS and whole blood Cytochrome P450 genotyping results

-          Investigate the feasibility of ICP-MS trace elemental analysis on DBS (exploratory)

-          Evaluate subject-, nurse-, and technician perception on DBS versus venous blood sampling