New concepts for personalized immunosuppression in the transplanted patient
Appears in the following Collection
- Farmasøytisk institutt 
AbstractAfter transplantation patients receive individualized immunosuppressive treatment based on drug concentrations to hinder rejection of the transplant. This thesis aimed to develop and apply alternative methods of measuring the immunosuppressants tacrolimus, belatacept and mycophenolic acid. Tacrolimus exerts its effect inside lymphocytes but is measured in whole blood. An assay developed in this thesis showed that concentrations inside lymphocytes was only partially related to the whole blood concentration. It was also shown that the amount of tacrolimus that distributes to lymphocytes after dose may decrease during the first year after transplantation. A belatacept assay was developed and used to show that belatacept has a stable pharmacokinetic profile, but heavier patients may have a higher drug exposure since belatacept dose is adjusted according to body mass. The pharmacodynamic response of mycophenolic acid was measured in resting and ex vivo stimulated lymphocytes. Mycophenolic acid had a stronger effect on stimulated cells, but in a cohort of transplant patient both resting and stimulated cells appeared to become less sensitive during the first year after transplantation.
List of papers
|Paper I. RA Klaasen, S Bergan, S Bremer, L Daleq, AM Andersen, K Midtvedt, MH Skauby, NT Vethe. Longitudinal Study of Tacrolimus in Lymphocytes During the First Year After Kidney Transplantation. Ther Drug Monit 2018; 40: 558-566. doi: 10.1097/FTD.0000000000000539. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1097/FTD.0000000000000539|
|Paper II. RA Klaasen, EJ Egeland, J Chan, K Midtvedt, K, M Svensson, N Bolstad, B Fellstrom, H Haldaas, A Åsberg, S Bergan, NT Vethe, DJ Warren. A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. Ther Drug Monit 2019; 41: 11-18. doi: 10.1097/FTD.0000000000000580. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1097/FTD.0000000000000580|
|Paper III. RA Klaasen, S Bergan, S Bremer, K Hole, C Nordahl, AM Andersen, K Midtvedt, MH Skauby, NT Vethe. Pharmacodynamic assessment of mycophenolic acid in resting and activated target cell population during the first year after renal transplantation. Br J Clin Pharmacol 2019; published online ahead of print, 2020 Jan 11. DOI: 10.1111/bcp.14218. The article is included in the thesis. Also available at: https://doi.org/10.1111/bcp.14218|