Immunosuppression, the art of suppressing the endogenous immune system to allow organ transplantation or treatment of autoimmune disease, is a clinico-pharmacological field that has markedly developed over the past three decades with the advent of highly potent and rationally targeted immunosuppressive agents. Pharmacogenomics, the art of providing tailored pharmacological therapy with the highest therapeutic index based on the genomic composition of the individual, is a science that has rapidly developed over the past decade, along with the advances in the human genome project and in biotechnology. Pharmacogenomics of immunosuppression is the combined art of tailoring specific immunosuppressive drug therapy to specific immune-mediated clinical entities which require immunosuppression, with optimum matching of the drug to the individual's genomic makeup. Timely and judicious application of pharmacogenomics to clinical immunosuppression should direct the clinician to the best immunosuppressive drug for any given clinical condition, and markedly increase its efficacy as well as decreasing the incidence of side effects and toxicity, thereby decreasing morbidity and prolonging survival. Is this a description of an ongoing clinical evolution in immunosuppression or a prediction of future events? The promises of pharmacogenomics of immunosuppression are high, yet the availability and/or application and/or realization of the promises of this highly specialized clinical science are very slow to come.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1517/phgs.4.3.309.22690 | DOI Listing |
Clin Transplant
February 2025
Excellence Center for Organ Transplantation, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Since 1987, King Chulalongkorn Memorial Hospital (KCMH) has performed a substantial number of heart transplants as a specific therapy for advanced-stage heart failure. This descriptive study aimed to analyze post-transplant survival in the recent era compared to earlier periods and examine the pharmacogenetics of related immunosuppressants. Data from all recipients who underwent heart transplants from 1987 to 2021 were retrospectively retrieved from the electronic medical record.
View Article and Find Full Text PDFCurr Issues Mol Biol
December 2024
Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA.
Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias.
View Article and Find Full Text PDFTher Drug Monit
February 2025
Biopharmaceutics and Pharmacokinetics Unit, Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
Different polymorphisms in genes encoding metabolizing enzymes and drug transporters have been associated with tacrolimus pharmacokinetics. In particular, studies on CYP3A4 and CYP3A5, and their combined cluster have demonstrated their significance in adjusting tacrolimus dosing to minimize under- and overexposure thereby increasing the proportion of patients who achieve tacrolimus therapeutic target. Many factors influence the pharmacokinetics of tacrolimus, contributing to inter-patient variability affecting individual dosing requirements.
View Article and Find Full Text PDFPharmacotherapy
January 2025
Texas Children's Cancer and Hematology Centers, Houston, Texas, USA.
Background: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.
Methods: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States.
Dent Med Probl
December 2024
Department of Cancer Prevention and Therapy, Wroclaw Medical University, Poland
Background: Multiple myeloma (MM) is a hematological malignancy characterized by the presence of abnormal plasma cells. It is associated with anemia, bone lesions and renal dysfunction. Immunomodulatory drugs (IMiDs) are commonly used in MM treatment.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!