Validation of PCR-Methods in a TDM-Laboratory

Therapeutic drug monitoring (TDM) is used to improve the benefit/risk ratio of drug treatment. We routinely use dose-related reference ranges to identify individual patients with abnormalities in drug metabolism, such as liver and/or kidney disease, drug-drug-interactions, and gene polymorphism; results are returned to the treating physician together with a clinical pharmacological comment [1]. Besides genotyping methods get more and more important in pharmacovigilance. We established several PCR-methods for genotyping of the most common cytochrome P450-isoenzymes in our TDM-laboratory. Our aim is to find out whether genotyping or determination of drug concentrations is more reliable in identifying poor and rapid drug metabolizers and in improving drug safety. For being able to offer genotyping as service for clinics and hospitals we want to validate the used methods (all taken from literature) for our lab. For these purposes we carried out the methods several times one after another, made by 3 different laboratory assistants all with the same DNA taken from 11 test persons, and compared the results. All colleagues achieved the same results with an accuracy of 94% and more. The here established methods are valid and sure for our TDM-laboratory routine.

Literature: [1] Haen E, Greiner C, Bader W, Wittmann M (2008): Wirkstoffkonzentrationsbestimmungen zur Therapieleitung – Ergaenzung therapeutischer Referenzbereiche durch dosisbezogene Referenzbereiche. Der Nervenarzt 79, 558–566.