Monitoring intracellular concentration and pharmacodynamic effects of tacrolimus in peripheral blood T CD4+ and B lymphocytes of kidney transplant recipients

• Grant number: 15/11389-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: July 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Nelson Zocoler Galante
• Grantee: Nelson Zocoler Galante
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Elias David-Neto ; Verônica Porto Carreiro de Vasconcellos Coelho

Abstract

Therapeutic drug monitoring (TDM) of immunosuppressive drugs is used to improve the immunosuppressive effect while minimizing the toxicity related to exposition to high serum levels. Although TDM is widely used in clinical practice, a significant number of kidney transplant recipients have acute allograft rejection in the first year after transplantation. To improve the use of immunosuppressive drugs, new approaches of TDM have been developed. Monitoring drug concentrations at lymphocytes of peripheral blood is considering promising because it indicates the availability of the drug directly in the target sites of immunosuppression.The present study intends to establish the concentration profile of tacrolimus in the peripheral blood in parallel with the concentration profile inside T and B lymphocytes of peripheral blood of kidney transplant recipients, and correlates them with the expected pharmacological effects. The pharmacological effects of tacrolimus in calcineurin dependent and calcineurin independent (MAPKs dependent) activation pathways will be assessed by measuring activated NFAT and p38, respectively, by flow cytometry. The expression of IL-2 and IL-10 by T and B lymphocytes, respectively, will be also used to monitoring the pharmacodynamic effects of tacrolimus. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROMANO, PASCHOALINA; FERNANDES, MARIA DA LUZ; REZENDE EBNER, PERSIO DE ALMEIDA; DE OLIVEIRA, NAYARA DUARTE; OKUDA, LARISSA MITSUE; AGENA, FABIANA; MENDES, MARIA ELIZABETE; SUMITA, NAIRO MASSAKAZU; COELHO, VERONICA; DAVID-NETO, ELIAS; et al. UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+and B CD19+lymphocytes. Journal of Pharmaceutical and Biomedical Analysis, v. 152, p. 306-314, APR 15 2018. (16/10083-9, 16/10043-7, 15/11389-1)