Pharmacogenetics and TDM in patients with long-acting injectable antipsychotics: First clinical experience

Geno- and phenotyping currently represent the main biological pillars for personalized medicine, particularly with regard to the prescription of psychotropic medications.. Nonetheless we are missing data regarding the usefulness of combining TDM with pharmacogenetics in patients treated with long-acting injectable antipsychotics (LAIs).

In a pilot projects we investigated the prevalence of individual variants of genes/polymorphisms involved in drug metabolism in LAI-treated patients. The catchment area of the Autonomous Province of Bolzano/Bozen counts 520.000 inhabitants For pharmacogenetic testing (PGx) the following methods were used: qPCR, digital PCR and DNA sequencing to determine >3360 SNPs in 24 genes. 138 SNPs from 12 phase I enzymes (CYP2C19, CYP2D6, CYP2C9, CYP3A4, CYP3A5, CYP2A6, CYP2B6, CYP2C8, CYP2E1, CYP1A2, DPYD and G6PD), 20 SNPs from 4 phase II enzymes (UGT1A1, UGT2B 15, NAT2 and TPMT), 7 SNPs from 1 transporter(s) (SLCO1B1), 5 SNPs from 1 transporter(s) (ABCB1(MDR1)) and 9 SNPs from 6 proteins (GSTP1, HLA-B*58:01, HLA-B* 15:02, HLA-A*31:01, HLA-B*57:01 and POLG) that are involved in drug metabolism and transport or associated with drug action. Phenotype prediction was based on in-depth knowledge of knowledge bases and Pharmgenetix internal laboratory research (published and available online: www.Pharmgenetix.com). Furthermore as a secondary objective we aimed to evaluate the association between the identified individual variants of genes/polymorphisms and TDM in these subjects.

Additionally to the study design the talk will provide further analysis regarding epidemiological distributions in the Autonomous Province of Bolzano/Bozen mainly in LAI-treated patients as well as first experiences in a case series' manner adopting a combination for TDM and genotyping for LAIs.

Publikationsverlauf

Artikel online veröffentlicht:
12. März 2024