Clinical pharmacokinetics in infectious diseases

• Grant number: 18/05616-3
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2019
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Vera Lúcia Lanchote
• Grantee: Vera Lúcia Lanchote
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Eduardo Barbosa Coelho
• Associated researchers: Geraldo Duarte ; Guilherme Suarez Kurtz ; Lauro Wichert Ana ; Marcelo Dias Baruffi ; Oscar Della Pasqua ; Rosamar Eulira Fontes Rezende ; Silvia Regina Cavani Jorge Santos ; Valdes Roberto Bollela
• Associated research grant(s): 19/08639-7 - Study of the frequency of polymorphisms in genes relevant to pharmacogenetics in a sample of Peruvians residing in dwellings located at different altitudes, AP.R SPRINT
• Associated scholarship(s): 23/04443-6 - Influence of pyelonephritis in pregnant women on the activity of membrane transporters OATP1B1 and OCT2, BP.DR; 22/16668-0 - Pharmacogenomics of blood-brain barrier transporters: impact of ABCB1, ABCG2 and OATP1A2 transporters on the pharmacokinetics of amphotericin B in patients undergoing treatment for neurocryptococcosis, BP.IC; 22/10335-9 - Pharmacokinetic-pharmacodynamic models (PK-PD) in macrophages and tuberculosis patients with application in personalized dose of rifampicin, isoniazid, pyrazinamide and ethambutol, BP.IC; + associated scholarships 22/09254-4 - Population pharmacokinetics in patients with infectious diseases, BP.PD; 21/00351-4 - Impact of pyelonephritis on the activity of organic anion transporters (OAT) 1 and 3 in pregnant women: a quantitative approach to systems pharmacology, BP.IC; 19/13401-0 - Influence of pregnancy associated with HIV on the activity of P-gp, BCRP and OATP drug transporters in women under Raltegravir treatment, BP.IC; 19/03429-4 - Pyelonephritis impacts on Organic Anion Transporters (OAT) 1 and 3 activity in pregnant women: a quantitative system pharmacology approach, BP.DR; 16/23938-2 - Influence of pregnancy associated with HIV on the activity of OATP drug transporter in patients under treatment with Efavirenz, BP.PD; 16/05624-0 - Pharmacokinetic-pharmacodynamic models (PK-PD) in macrophages and tuberculosis patients with application in personalized dose of rifampicin, isoniazid, pyrazinamide and ethambutol, BP.PD - associated scholarships

Abstract

The present project brings together clinical pharmacokinetics and pharmacogenetics studies in infectious diseases caused by bacteria, parasites or viruses, in which the inflammatory component is predominant. Subproject 1 elaborates pharmacokinetic-pharmacodynamic (PK-PD) models of antibiotics in patients with tuberculosis including data from plasma and macrophages infected with M. tuberculosis strains. Subproject 2 evaluates the influence of chronic hepatitis C on the CYP2A9, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 activity and on the BCRP, OATP1B1, OCT1 and P-gp transporters in patients with different degrees of hepatic fibrosis, covering the prediction of drug-disease interactions. Subproject 3 evaluates the influence of pregnancy associated with HIV on the activity of the P-gp, BCRP and OATP transporters in patients receiving raltegravir, using pharmacokinetic model based on physiology (PBPK) in order to identify the variability in PK of raltegravir during pregnancy. Subproject 4 elaborates PK-PD models for antimicrobials in burn patients in sepsis including plasma exposure data and activity of these agents in vitro-in vivo, allowing the initial dose to be replaced by the adjusted dose. Subproject 5 investigates the phenotypic activity of the enzymes CYP2A9, CYP2C9, CYP2C19, CYP3A4 and CYP2D6 in patients with Plasmodium vivax malaria, allowing the evaluation of the risk of inefficacy or toxicity of medicines as a consequence of pharmacokinetic changes associated with the disease parasitic infection. Subproject 6 evaluates the integrity of the blood-brain barrier using SPECT with 99mTc-DTPA and the monitoring of CSF amphotericin B concentrations in patients with neurocryptococcosis, using PBPK as a prediction model. The data obtained in the six subprojects will be applied in precision medicine. (AU)

Scientific publications

(12)

(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)

RIBEIRO PINTO, LEONARDO SANTOS; DO VALE, GABRIEL TAVARES; MOREIRA, FERNANDA DE LIMA; MARQUES, MARIA PAULA; COELHO, EDUARDO BARBOSA; CAVALLI, RICARDO CARVALHO; LANCHOTE, VERA LUCIA. Direct chiral LC-MS/MS analysis of fexofenadine enantiomers in plasma and urine with application in a maternal-fetal pharmacokinetic study. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v. 1145, MAY 15 2020. (18/05616-3)

BENZI, JHOHANN RICHARD DE LIMA; ROCHA, ADRIANA; COLOMBARI, JULIA CRISTINA; PEGO, ALEF MACHADO GOMES; MELLI, PATRICIA PEREIRA DOS SANTOS; DUARTE, GERALDO; LANCHOTE, VERA LUCIA. Determination of furosemide and its glucuronide metabolite in plasma, plasma ultrafiltrate and urine by HPLC-MS/MS with application to secretion and metabolite formation clearances in non-pregnant and pregnant women. Journal of Pharmaceutical and Biomedical Analysis, v. 235, p. 9-pg., 2023-10-25. (21/10292-5, 18/05616-3, 21/00351-4, 19/03429-4)

THOMAZ, MATHEUS DE LUCCA; VIEIRA, CAROLINA PINTO; CARIS, JUCIENE APARECIDA; MARQUES, MARIA PAULA; ROCHA, ADRIANA; PAZ, TIAGO ANTUNES; REZENDE, ROSAMAR EULIRA FONTES; LANCHOTE, VERA LUCIA. Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients. PHARMACEUTICALS, v. 17, n. 7, p. 14-pg., 2024-07-01. (18/05616-3)

MATSUNO, VICTOR KANEKO; DE CAMPOS, EDVALDO VIEIRA; DA SILVA JUNIOR, ELSON MENDES; DA SILVA JUNIOR, JOAO MANOEL; GOMEZ, DAVID DE SOUZA; SANTOS, SILVIA REGINA CAVANI JORGE. Changes in fl uconazole pharmacokinetics can impact on antifungal effectiveness in critically ill burn patients: a PharmacokineticPharmacodynamic (PK/PD) approach. Clinics, v. 79, p. 7-pg., 2024-09-23. (18/05616-3)

NARDOTTO, GLAUCO HENRIQUE BALTHAZAR; BOLLELA, VALDES ROBERTO; ROCHA, ADRIANA; DELLA PASQUA, OSCAR; LANCHOTE, VERA LUCIA. No implication of HIV coinfection on the plasma exposure to rifampicin, pyrazinamide, and ethambutol in tuberculosis patients. CTS-CLINICAL AND TRANSLATIONAL SCIENCE, OCT 2021. (18/05616-3, 16/05624-0)

MOREIRA, FERNANDA DE LIMA; DOS SANTOS MELLI, PATRICIA PEREIRA; MARQUES, MARIA PAULA; ROCHA, ADRIANA; BALTHAZAR NARDOTTO, GLAUCO HENRIQUE; DUARTE, GERALDO; LANCHOTE, VERA LUCIA. P-Glycoprotein and Organic Anion Transporter Polypeptide 1B/Breast Cancer Resistance Protein Drug Transporter Activity in Pregnant Women Living With HIV. Journal of Clinical Pharmacology, v. 63, n. 2, p. 9-pg., 2022-10-04. (16/23938-2, 18/05616-3)

MOREIRA, FERNANDA DE LIMA; MARQUES, MARIA PAULA; DUARTE, GERALDO; LANCHOTE, VERA LUCIA. Determination of raltegravir and raltegravir glucuronide in human plasma and urine by LC-MS/MS with application in a maternal-fetal pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis, v. 177, JAN 1 2020. (18/05616-3, 16/23938-2)

DE LIMA BENZI, JHOHANN RICHARD; MOREIRA, FERNANDA DE LIMA; MARQUES, MARIA PAULA; DUARTE, GERALDO; SUAREZ-KURTZ, GUILHERME; LANCHOTE, VERA LUCIA. A background subtraction approach for determination of endogenous cortisol and 6 beta-hydroxycortisol in urine by UPLC-MS/MS with application in a within-day variability study in HIV-infected pregnant women. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v. 1144, MAY 1 2020. (19/03429-4, 18/05616-3, 16/23938-2)

NARDOTTO, GLAUCO HENRIQUE BALTHAZAR; SVENSON, ELIN M.; BOLLELA, VALDES ROBERTO; ROCHA, ADRIANA; SLAVOV, SVETOSLAV NANEV; XIMENEZ, JOAO PAULO BIANCHI; DELLA PASQUA, OSCAR; LANCHOTE, VERA LUCIA. Effect of Interindividual Variability in Metabolic Clearance and Relative Bioavailability on Rifampicin Exposure in Tuberculosis Patients with and without HIV Co-Infection: Does Formulation Quality Matter?. PHARMACEUTICS, v. 16, n. 8, p. 14-pg., 2024-08-01. (18/05616-3, 16/05624-0)

MOREIRA, FERNANDA DE LIMA; BENZI, JHOHANN RICHARD DE LIMA; PINTO, LEONARDO; THOMAZ, MATHEUS DE LUCCA; DUARTE, GERALDO; LANCHOTE, VERA LUCIA. Optimizing Therapeutic Drug Monitoring in Pregnant Women: A Critical Literature Review. THERAPEUTIC DRUG MONITORING, v. 45, n. 2, p. 14-pg., 2023-04-01. (16/23938-2, 18/05616-3)

PIPPA, LEANDRO FRANCISCO; VIEIRA, CAROLINA PINTO; CARIS, JUCIENE APARECIDA; ROCHA, ADRIANA; MARQUES, MARIA PAULA; GARCIA, CAMILE PRATES; REZENDE, ROSAMAR EULIRA FONTES; LANCHOTE, VERA LUCIA. Effect of Chronic Hepatitis C on the Activity of the Membrane Transporters P-gp and OATP1B1/BCRP on Patients With Different Stages of Hepatic Fibrosis. CLINICAL PHARMACOLOGY & THERAPEUTICS, v. 114, n. 1, p. 9-pg., 2023-05-16. (18/05616-3)

MOREIRA, FERNANDA DE LIMA; PAZ, TIAGO ANTUNES; MELLI, PATRICIA PEREIRA DOS SANTOS; THOMAZ, MATHEUS DE LUCCA; MARQUES, MARIA PAULA; ROCHA, ADRIANA; DUARTE, GERALDO; LANCHOTE, VERA LUCIA. Total, Unbound, Renal, and Hepatic Clearances of Raltegravir and the Formation and Elimination Clearances of Raltegravir Glucuronide in Pregnant Women. Journal of Clinical Pharmacology, v. N/A, p. 8-pg., 2023-06-20. (16/23938-2, 18/05616-3)