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Metabolism of dapaconazole

Grant number: 16/22506-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2017
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Gilberto de Nucci
Grantee:Natalícia de Jesus Antunes
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):19/03905-0 - Development and validation of a combined LC-MS/MS assay for determination of sirolimus, everolimus, tacrolimus and ciclosporin in whole blood., BE.EP.PD

Abstract

Resistance to treatment with antifungal agents is increasing and evolving, complicating the treatment of fungal infections, which has also grown significantly in recent decades. The dapaconazole tosylate, a new antifungal imidazole, with powerful effect on a wide variety of pathogenic fungi may be a viable alternative to combat this problem. Thus, this study aims to elucidate the in vitro and in vivo metabolism of dapaconazol, as well as drug-drug interaction. In vitro identification of dapaconazole metabolites, the study of its metabolic stability and of the CYP450 induction will be performed using human, Beagle dogs cryopreserved hepatocytes, and for the investigation of CYP450 inhibition human and Beagle dogs microsomes will be used. The in vivo metabolism will be conducted in Beagle dogs. The determination of analytes will be performed by high-performance liquid chromatography (HPLC) and by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). (AU)

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Scientific publications (10)
(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)
CAMPOS, RAFAEL; ARAUJO PINHEIRO, DAVID HALEN; BRITTO-JUNIOR, JOSE; DE CASTRO, HELESON ALVES; MENDES, GUSTAVO DUARTE; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; BRANDAO LOPES-MARTINS, RODRIGO ALVARO; ANTUNES, NATALICIA J.; DE NUCCI, GILBERTO. Quantification of 6-nitrodopamine in Krebs-Henseleit's solution by LC-MS/MS for the assessment of its basal release from Chelonoidis carbonaria aortae in vitro. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v. 1173, MAY 30 2021. Web of Science Citations: 0.
ANTUNES, NATALICIA J.; KIPPER, KARIN; COUCHMAN, LEWIS; DUNCAN, MARIE-ANNE; HOLT, DAVID W.; DE NUCCI, GILBERTO; JOHNSTON, ATHOLL. Simultaneous quantification of cyclosporin, tacrolimus, sirolimus and everolimus in whole blood by UHPLC-MS/MS for therapeutic drug monitoring. BIOMEDICAL CHROMATOGRAPHY, v. 35, n. 6 FEB 2021. Web of Science Citations: 1.
DE JESUS ANTUNES, NATALICIA; DE OLIVEIRA FILHO, RAIMUNDO VIEIRA; DE OLIVEIRA ILHA, JAIME; MORENO, RONILSON A.; NAHOUM, ANDRE FELIPE; WEDEMEYER, RALPH-STEVEN; WARNKE, ANDRE; DE NUCCI, GILBERTO. Single-dose pharmacokinetics and pharmacodynamics assessment of oestriol and trimegestone containing vaginal rings in healthy women with childbearing potential. EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE, v. 26, n. 3 FEB 2021. Web of Science Citations: 0.
ANTUNES, NATALICIA J.; INCE, NINA; RAYMOND, JASON; KIPPER, KARIN; COUCHMAN, LEWIS; HOLT, DAVID W.; DE NUCCI, GILBERTO; JOHNSTON, ATHOLL. Quantification of mycophenolic acid in human plasma by liquid chromatography with time-of-flight mass spectrometry for therapeutic drug monitoring. BIOMEDICAL CHROMATOGRAPHY, v. 35, n. 3 NOV 2020. Web of Science Citations: 0.
BRITTO-JUNIOR, JOSE; ANTUNES, NATALICIA J.; CAMPOS, RAFAEL; SUCUPIRA, MAURO; MENDES, GUSTAVO DUARTE; FERNANDES, FERNANDA; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; DE NUCCI, GILBERTO. Determination of dopamine, noradrenaline, and adrenaline in Krebs-Henseleit solution by liquid chromatography coupled with tandem mass spectrometry and measurement of their basal release fromChelonoidis carbonariaaortaein vitro. BIOMEDICAL CHROMATOGRAPHY, v. 35, n. 2 SEP 2020. Web of Science Citations: 1.
KIPPER, KARIN; HECHT, MAX; ANTUNES, NATALICIA J.; FAIRBANKS, LYNETTE D.; LEVENE, MICHELLE; UCAR, SEMA KALKAN; SCHAEFER, ANDREW; BLAKELY, EMMA L.; BAX, BRIDGET E. Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy. JOURNAL OF CLINICAL MEDICINE, v. 9, n. 3 MAR 2020. Web of Science Citations: 0.
GOBBATO, CINTIA; GOBBATO, ANDRE; MAGALHAES, TAINAH B.; MENDES, GUSTAVO D.; ILHA, JAIME O.; MORENO, RONILSON A.; ANTUNES, NATALICIA J.; DE NUCCI, GILBERTO. Randomized, double-blind, phase III clinical study of a novel nanotechnological topical anesthetic formulation containing lidocaine 25 mg/g and prilocaine 25 mg/g (nanorap) in skin phototypes I-III patients with ablative fractional CO2 laser treatment indication in the forehead. Lasers in Surgery and Medicine, v. 51, n. 7, p. 609-615, SEP 2019. Web of Science Citations: 2.
JACOB, JULIANA DE MORAES; ANTUNES, NATALICIA DE JESUS; MORENO, RONILSON; DE NUCCI, GILBERTO. Evaluation of folic acid supplementation by concomitant administration of ethinyl estradiol plus levonorgestrel in healthy female subjects. INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, v. 57, n. 6, p. 290-297, JUN 2019. Web of Science Citations: 0.
SEVERINO, BEATRICE; CORVINO, ANGELA; FIORINO, FERDINANDO; FRECENTESE, FRANCESCO; PERISSUTTI, ELISA; CALIENDO, GIUSEPPE; SANTAGADA, VINCENZO; MAGLI, ELISA; MOLINARO, PASQUALE; PIGNATARO, GIUSEPPE; ANNUNZIATO, LUCIO; ANTUNES, NATALICIA J.; ROJAS-MOSCOSO, JULIO; DE FREITAS, NOEDI L.; MENDES, GUSTAVO D.; DE NUCCI, GILBERTO. Development, Validation of LC-MS/MS Method and Determination of Pharmacokinetic Parameters of the Stroke Neuroprotectant Neurounina-1 in Beagle Dog Plasma After Intravenous Administration. FRONTIERS IN PHARMACOLOGY, v. 10, APR 25 2019. Web of Science Citations: 1.
DE OLIVEIRA FILHO, RAIMUNDO VIEIRA; ANTUNES, NATALICIA DE JESUS; ILHA, JAIME DE OLIVEIRA; MORENO, RONILSON AGNALDO; WEDEMEYER, RALPH-STEVEN; WARNKE, ANDRE; DE NUCCI, GILBERTO. Pharmacokinetics and pharmacodynamics of three dosages of oestriol after continuous vaginal ring administration for 21 days in healthy, postmenopausal women. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, v. 85, n. 3, p. 551-562, MAR 2019. Web of Science Citations: 0.

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