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Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy

Grant number: 17/11516-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2017
Effective date (End): April 30, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Eloisa Silva Dutra de Oliveira Bonfá
Grantee:Julio Cesar Rente Ferreira Filho
Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy, AP.TEM


No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. There is also a large inter-individual variability in response to treatments with regard to efficacy and toxicity, and for many drugs, there is also a period of weeks to months to establish its efficacy. Within this context, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide, glucocorticoids, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. The implementation of this methodology dedicated to research in our center, with the necessary training of human resources, will enable the standardization and availability of this advanced technology to other muldisciplinary projects in various areas of science. For biological agents the focus will be on the understanding the loss of efficacy and the possible role of anti-TNF antibodies using ELISA capture methodology.This thematic project will be divided into four sections with their respective sub-projects according to the medications that will be studied: hydroxychloroquine, thalidomide, biologic agents and glucocorticoids

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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)
PEDROSA, TATIANA N.; PASOTO, SANDRA G.; AIKAWA, NADIA E.; YUKI, EMILY F. N.; BORBA, EDUARDO F.; FERREIRA FILHO, JULIO C. R.; CARRICONDO, PEDRO C.; ZANETTI, CAIO B.; CONDE, PAOLA G.; DUARTE, NILO J. C.; et al. Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis. Lupus, v. 29, n. 6, . (15/03756-4, 17/11516-9, 17/11854-1, 17/14352-7, 17/11644-7)
DUARTE, NILO J. C.; KUPA, LEONARD V. K.; FERREIRA-FILHO, JULIO C. R.; FONTOURA, NICOLE; CHALOM, MARC Y.; ROMANO, PASCHOALINA; EBNER, PERSIO A. R.; SILVA, CLOVIS A. A.; CARVALHO, VALDEMIR M.; BONFA, ELOISA. UHPLC-MS/MS Method for Determination of Hydroxychloroquine and Its Main Metabolites in Oral Fluid and Whole Blood for Therapeutic Drug Monitoring. JOURNAL OF APPLIED LABORATORY MEDICINE, v. 6, n. 4, p. 868-880, . (15/03756-4, 17/11644-7, 17/11516-9, 19/17272-0, 17/03983-6)
TONACIO, ADRIANA CORACINI; PEDROSA, TATIANA DO NASCIMENTO; BORBA, EDUARDO FERREIRA; AIKAWA, NADIA EMI; PASOTO, SANDRA GOFINET; RENTE FERREIRA FILHO, JULIO CESAR; SAMPAIO BARROS, MARILIA MANTOVANI; LEON, ELAINE PIRES; FERREIRA SPINA LOMBARDI, SUZETE CLEUSA; MENDRONE JUNIOR, ALFREDO; et al. mmunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic disease. PLoS Neglected Tropical Diseases, v. 15, n. 11, . (10/10749-0, 17/14352-7, 18/16162-3, 17/11516-9)

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