Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in renal transplantation
| Autor: | Takafumi Kuzuya, Yoshihiko Watarai, Akio Katayama, Takaaki Kobayashi, Kazuharu Uchida, Yuko Miwa, Kiyofumi Yamada, Kenta Iwasaki, Masataka Haneda, Katsuo Amioka, Yoko Kurata |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Graft Rejection Male Herpesvirus 3 Human T-Lymphocytes medicine.medical_treatment Immunology Cytomegalovirus Pharmacology Carboxyfluorescein diacetate succinimidyl ester Antibodies Nephrotoxicity chemistry.chemical_compound HLA Antigens medicine Humans Immunology and Allergy Adverse effect medicine.diagnostic_test business.industry Immunosuppression Middle Aged Kidney Transplantation Transplantation chemistry Therapeutic drug monitoring Pharmacodynamics Toxicity Cyclosporine Female Kidney Diseases Virus Activation business Immunosuppressive Agents |
| Zdroj: | International Immunopharmacology. 22:384-391 |
| ISSN: | 1567-5769 |
| Popis: | Although therapeutic drug monitoring based on blood concentration has been widely implemented in transplant recipients treated with immunosuppressive agents, clinical adverse events such as rejection, infection or drug-induced toxicity caused by inappropriate dosage cannot be completely controlled. Development of an effective assay for optimized immunosuppression would be desirable, which can potentially lead to personalized medicine in renal transplantation. Cyclosporine (CSA) pharmacodynamic analysis using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based T cell proliferation assay was examined in 66 kidney transplant recipients before and after transplantation. Two parameters, the 50% inhibitory concentration (IC50) and the percentage of T-cell proliferation values at the lower plateau (bottom), were compared with clinical events. A significant relation in CSA pharmacodynamic parameters was observed between pre- and post-transplantation. Analysis of the association between clinical outcomes and pharmacodynamic parameters in post-transplant samples demonstrated the following findings: (i) cytomegalovirus (CMV)/varicella zoster virus (VZV) reactivation and CSA-induced nephrotoxicity were significantly associated with high sensitivity to CSA (low bottom or low IC50), (ii) acute T cell-mediated rejection (ATMR) was significantly related to low sensitivity to CSA (high bottom), and (iii) de novo human leukocyte antigen (HLA) antibody production was associated with lower bottom and IC50 values, although the elucidation of those mechanisms is still in progress. It was suggested that CSA pharmacodynamics applied at post-transplantation would be useful for optimizing immunosuppressive therapy. |
| Databáze: | OpenAIRE |
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