Benznidazole pharmacokinetics in patients with chronic Chagas disease: association with demographic factors and adverse drug reactions Gabriel P E Silveira, Luciana F Portela, Leticia B Saavedra, Filipe P Costa, Douglas P Pinto, et al. Journal of Antimicrobial Chemotherapy, 2026 Background The knowledge about benznidazole pharmacokinetics (PK) in patients with chronic Chagas disease (CD) is limited. Objective To evaluate the benznidazole PK parameters in patients with chronic CD, stratified by age, sex, and adverse drug reactions (ADRs) occurrence. Methods Single-centre, open-label, clinical trial that included adult patients with chronic CD who received benznidazole 300 mg/day for 60–80 days. Blood samples were collected on Days 1, 7, 15, 30, and 60 of treatment. Benznidazole was quantified by HPLC-MS/MS and PK analysis used non-compartmental analysis. Results Twenty-nine participants (16 females; 55.2%) were included. Five (17.2%) participants interrupted the treatment definitely due to ADRs. PK parameters after a single benznidazole dose were as follows: Cmax = 2.48(0.53) µg/mL, AUC0–6 = 10.80(2.59) h*µg/mL, and Tmax = 2.7(1.3) h. The steady-state PK parameters on Day 15 were as follows: Cmax,ss = 7.86(2.06) µg/mL, AUC0–6,ss = 42.05(10.87) h*µg/mL, and Tmax,ss = 2.3 (1.2 h). Tmax was longer among those ≥60 years old (P = 0.045), and Cmax (P = 0.0004) and AUC0–6 (P = 0.003) were higher in females, but PK parameters normalized by weight were similar between sexes. The most frequent ADRs were skin reactions (44.8%), gastrointestinal (37.9%), haematological (20.7%), and neurological (27.6%). Sex was associated with gastrointestinal ADRs, while weight was associated with skin reactions. Higher benznidazole plasma levels on Days 1, 7, and 15 of treatment were associated with skin reactions even adjusting for age and sex. Conclusions Benznidazole PK presented little variation according to sex and age, but differences in sex appeared linked to females lower weight. Higher benznidazole plasma levels were associated with skin reactions, indicating a potential dose-dependent relationship of this ADR. Trial registration This study was registered on the Brazilian Clinical Trials Database—REBEC (RBR-5vg8p36). Registered on 11 August 2021. https://ensaiosclinicos.gov.br/rg/RBR-5vg8p36.
Amikacin Dosing Adjustment in Critically Ill Oncologic Patients: A Study with Real-World Patients, PBPK Analysis, and Digital Twins Juliana Queiroz da Silva, Natália Valadares de Moraes, Rita Estrela, Diogenes Coelho, Diego Feriani, et al. Pharmaceutics, 2025 Background/Objectives: Guidelines recommend adjusting amikacin dosing based on patients’ renal function. Nevertheless, for critically ill cancer patients, the renal function equations based on serum creatinine levels have low or no correlation with amikacin clearance. Considering this, using real-world data, we built an amikacin PBPK model to predict amikacin plasma concentrations in critically ill oncologic patients stratified by renal impairment levels. Further, the model was applied for dose stratification and individualization (digital twin strategy) in this population. Methods: In the Therapeutic Drug Monitoring (TDM) study, 368 amikacin pharmacokinetic analyses from 184 critically ill cancer patients were enrolled in three cohorts. A full-body PBPK model was developed using PK-Sim v. 11.3. Results: The final PBPK model accounted for two groups of critically ill cancer patients with mild (creatinine clearance; CLcr ≥ 60 mL/min) or severe (CLcr < 60 mL/min) renal dysfunction. In the dose stratification strategy, at the 7th dose, cancer patients with CLcr ≥ 60 mL/min under regimens 20 mg/kg (q24h); 25 mg/kg (q24h); 25 mg/kg (q48h); and 30 mg/kg (q72h) have probability of ≥69% of the patients achieving the efficacy target (AUC/MIC > 80, MIC of 4 mg/L), while cancer patients with CLcr < 60 mL/min under regimens 7.5 mg/kg (q24h); 15 mg/kg (q24h); 15 mg/kg (q48h); and 20 mg/kg (q36h) have ≥90% probability of achieving the same efficacy target. Conclusions: Our MIPD approach demonstrates potential in optimizing amikacin dosing for critically ill cancer patients. However, it does not eliminate the need for TDM due to unexplained variability still not accounted for by the PBPK model.
A Narrative Review of Chromatographic Bioanalytical Methods for Quantifying Everolimus in Therapeutic Drug Monitoring Applications Julia O. Nascimento, Edlaine R. Costa, Rita Estrela, Fernanda L. Moreira Therapeutic Drug Monitoring, 2025 Background: Methods for measuring drug levels in the body are crucial for improving therapeutic drug monitoring (TDM) and personalized medicine. In solid-organ transplants, TDM is essential for the management of immunosuppressive drugs to avoid toxicity and organ rejection. Everolimus is a commonly used immunosuppressant with a small range of safe doses; therefore, it is important to adjust the dose according to each patient's needs. Therefore, reliable methods are required to accurately measure everolimus levels. This study aims to conduct a comprehensive and updated narrative review of chromatographic bioanalytical methods for everolimus quantification. Methods: The authors searched for original research articles published between 2013 and 2023 in Scopus and PubMed and found 295 articles after removing duplicates. Based on their titles and summaries, 30 articles were selected for a detailed review and 25 articles were included in the final analysis. Results: Among the 25 studies, 16 used protein precipitation, mainly with methanol, to prepare the samples, 12 used high-performance liquid chromatography, 11 used ultra-performance liquid chromatography, and 2 used both. Almost all the studies (24 of 25) used tandem mass spectrometry for detection, whereas only 1 used ultraviolet. Conclusions: This comprehensive review of bioanalytical methods for measuring everolimus using chromatography is a useful resource for researchers developing bioanalytical methods for TDM applications. Future trends in everolimus measurement include achieving lower detection limits, owing to the trend of reducing drug doses in therapy by improving sample extraction techniques and using more sensitive methods.
Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil Robson Pierre Nascimento da Silva, Luana M. S. Marins, Lusiele Guaraldo, Paula Mendes Luz, Sandra W. Cardoso, et al. AIDS Research and Therapy, 2023 Background The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil. Methods Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy. Results A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4–54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2–17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2–52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy. Conclusions We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients’ therapeutic regimens should be implemented.
Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution V Santos, LR Dantas, GB Ortis, PH Suss, R Estrela, ER Costa, FL Moreira, ... 2026
Benznidazole pharmacokinetics in patients with chronic Chagas disease: association with demographic factors and adverse drug reactions GPE Silveira, LF Portela, LB Saavedra, FP Costa, DP Pinto, FM Carneiro, ... Journal of Antimicrobial Chemotherapy 81 (1), dkaf416 , 2026 2026
Transcriptional evaluation of functional genes of resistance, biofilm and quorum sensing in CTX-M15 ESBL-producing Klebsiella pneumoniae after meropenem concentration based on … S Carstensen, PH Suss, GB Ortis, R Estrela, ER Costa, FL Moreira, ... Research in Microbiology, 104304 , 2025 2025 Citations: 1
Disulfiram repurposing in the combined chemotherapy of Chagas disease: A protocol update for a phase I/II clinical trial RM Saraiva, LF Portela, GPE da Silveira, J de Araujo Frisso, FP da Costa, ... Medicine: Case Reports and Study Protocols 6 (3), e365 , 2025 2025 Citations: 2
Amikacin Dosing Adjustment in Critically Ill Oncologic Patients: A Study with Real-World Patients, PBPK Analysis, and Digital Twins JQ Silva, NV Moraes, R Estrela, D Coelho Jr, D Feriani, K Migotto, ... Pharmaceutics 17 (3), 297 , 2025 2025 Citations: 4
A Narrative Review of Chromatographic Bioanalytical Methods for Quantifying Everolimus in Therapeutic Drug Monitoring Applications JO Nascimento, ER Costa, R Estrela, FL Moreira Therapeutic Drug Monitoring 47 (1), 49-63 , 2025 2025 Citations: 4
Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV, Part II: Drugs Licensed Before 2005 T Toledo, VG Oliveira, VB Cattani, K Seba, VG Veloso, B Grinsztejn, ... Clinical Pharmacokinetics 63 (12), 1655-1666 , 2024 2024 Citations: 1
Frailty and health-related quality of life among older people living with HIV pre-and post-COVID-19 pandemic onset: A cross-sectional study TS Torres, JS Jesus, D Arabe, L Guaraldo, FA Meque, FS Lessa, ... The Brazilian Journal of Infectious Diseases 28 (1), 103723 , 2024 2024 Citations: 4
The effect of dietary fibers on the absorption of oral hypoglycemic drugs: a systematic review of controlled trials ER Costa, TN Castro, R de Cássia Elias Estrela, JCS Gonçalves, G Rosa International Journal of Diabetes in Developing Countries 43 (5), 631-640 , 2023 2023
Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review: T. Toledo et al. T Toledo, T Castro, VG Oliveira, VG Veloso, B Grinsztejn, SW Cardoso, ... Clinical Pharmacokinetics 62 (9), 1219-1230 , 2023 2023 Citations: 9
Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil RPN da Silva, LMS Marins, L Guaraldo, PM Luz, SW Cardoso, RI Moreira, ... AIDS Research and Therapy 20 (1), 57 , 2023 2023 Citations: 3
Estradiol and Spironolactone Plasma Pharmacokinetics Among Brazilian Transgender Women Using HIV Pre-Exposure Prophylaxis: Analysis of Potential Interactions: VB Cattani et al. VB Cattani, EM Jalil, L Eksterman, T Torres, S Wagner Cardoso, ... Clinical pharmacokinetics 62 (7), 1031-1041 , 2023 2023 Citations: 8
Development and validation of liquid chromatography-tandem mass spectrometry method to quantify dasatinib in plasma and its application to a pharmacokinetic study ER Costa, TN Castro, CF Gonçalves-de-Albuquerque, HCC Faria Neto, ... Brazilian Journal of Pharmaceutical Sciences 59, e21415 , 2023 2023 Citations: 1
Development and validation of LC–MS/MS methods for the simultaneous quantification of sofosbuvir and its major metabolite (GS‐331007) in blood plasma and cerebrospinal and … LS Vilhena, AC de Azevedo da Silva, DM dias da Silva, DP Pinto, ... Biomedical Chromatography 37 (5), e5606 , 2023 2023 Citations: 2
Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: a nested drug–drug interaction study in a cohort of Brazilian transgender women … RE Vitória Berg Cattani, Emilia Moreira Jalil, Leonardo Eksterman, Thiago ... Journal of Antimicrobial Chemotherapy 77 (10), 2729–2736 , 2022 2022 Citations: 13
Low PrEP adherence despite high retention among transgender women in Brazil: the PrEParadas study EM Jalil, TS Torres, PM Luz, L Monteiro, RI Moreira, CRV de Castro, ... Journal of the International AIDS Society 25 (3), e25896 , 2022 2022 Citations: 56
Population pharmacokinetics of tenofovir/emtricitabine among transwomen at HIV risk on oral prep and feminizing hormone therapy: Analysis of potential interactions on prep VB Cattani, EM Jalil, L Eksterman, T Torres, SW Cardoso, C Castro, ... Revista Colombiana de Ciencias Químico-Farmacéuticas 51 (3), 1586-1587 , 2022 2022
Extended stability study of an extemporaneously analgesic solution of clonidine, ropivacaine and fentanyl AM Oliveira, JCS Gonçalves, RCE Estrela Brazilian Journal of Pharmaceutical Sciences 58, e191121 , 2022 2022
No impact of tenofovir/emtricitabine in estradiol exposure among transwomen on oral PrEP: results from the 12-week drug-drug interaction PrEParadas substudy. V Cattani, E Jalil, T Torres, S Cardoso, L Eksterman, C Castro, L Monteiro, ... Journal of the International AIDS Society 24 (S4), 30-32 , 2021 2021 Citations: 2
Disulfiram repurposing in the combined chemotherapy of Chagas disease: A protocol for phase I/II clinical trial RM Saraiva, LF Portela, GPE da Silveira, NL da Silva Gomes, DP Pinto, ... Medicine: Case Reports and Study Protocols 2 (7), e0110 , 2021 2021 Citations: 16
MOST CITED SCHOLAR PUBLICATIONS
Retention, engagement, and adherence to pre-exposure prophylaxis for men who have sex with men and transgender women in PrEP Brasil: 48 week results of a demonstration study B Grinsztejn, B Hoagland, RI Moreira, EG Kallas, JV Madruga, S Goulart, ... The lancet HIV 5 (3), e136-e145 , 2018 2018 Citations: 223
The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV‐infected men FB Kohlrausch, R de Cássia Estrela, PF Barroso, G Suarez‐Kurtz British journal of clinical pharmacology 69 (1), 95-98 , 2010 2010 Citations: 95
A rapid and sensitive method for simultaneous determination of lamivudine and zidovudine in human serum by on‐line solid‐phase extraction coupled to liquid chromatography … RCE Estrela, MC Salvadori, G Suarez‐Kurtz Rapid communications in mass spectrometry 18 (10), 1147-1155 , 2004 2004 Citations: 65
Low PrEP adherence despite high retention among transgender women in Brazil: the PrEParadas study EM Jalil, TS Torres, PM Luz, L Monteiro, RI Moreira, CRV de Castro, ... Journal of the International AIDS Society 25 (3), e25896 , 2022 2022 Citations: 56
Determination of lopinavir and ritonavir in blood plasma, seminal plasma, saliva and plasma ultra‐filtrate by liquid chromatography/tandem mass spectrometry detection RCE Estrela, FS Ribeiro, BV Seixas, G Suarez‐Kurtz Rapid Communications in Mass Spectrometry: An International Journal Devoted … , 2008 2008 Citations: 53
Distribution of ABCB1 Polymorphisms Among Brazilians: Impact of Population Admixture RCE Estrela, FS Ribeiro, RS Carvalho, SP Gregorio, E Dias-Neto, ... Pharmacogenomics 9 (3), 267-276 , 2008 2008 Citations: 52
A rapid and simple HPLC method for therapeutic monitoring of vancomycin TM Lima, KS Seba, JCS Gonçalves, FLL Cardoso, RCE Estrela Journal of chromatographic science 56 (2), 115-121 , 2018 2018 Citations: 47
ABCB1 Polymorphisms and the Concentrations of Lopinavir and Ritonavir in Blood, Semen and Saliva of HIV-Infected Men under Antiretroviral Therapy RC Estrela, FS Ribeiro, PF Barroso, M Tuyama, SP Gregório, E Dias-Neto, ... Pharmacogenomics 10 (2), 311-318 , 2009 2009 Citations: 43
CYP3A5 Genotype Has No Impact on Plasma Trough Concentrations of Lopinavir and Ritonavir in HIV‐infected Subjects RCE Estrela, AB Santoro, PF Barroso, M Tuyama, G Suarez‐Kurtz Clinical Pharmacology & Therapeutics 84 (2), 205-207 , 2008 2008 Citations: 35
The Yin and Yang of tyrosine kinase inhibition during experimental polymicrobial sepsis CF Gonçalves-de-Albuquerque, I Rohwedder, AR Silva, AS Ferreira, ... Frontiers in immunology 9, 901 , 2018 2018 Citations: 34
Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone G Suarez-Kurtz, FM Ribeiro, RCE Estrela, FL Vicente, CJ Struchiner Brazilian journal of medical and biological research 34 (11), 1475-1485 , 2001 2001 Citations: 27
Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST EA Santos, JCS Gonçalves, MK Fleury, AL Kritski, MM Oliveira, ... The Brazilian Journal of Infectious Diseases 23 (6), 381-387 , 2019 2019 Citations: 25
Determination of stavudine in human serum by on‐line solid‐phase extraction coupled to high‐performance liquid chromatography with electrospray ionization tandem mass … RSL Raices, MC Salvadori, RCE Estrela, FRA Neto, G Suarez‐Kurtz Rapid communications in mass spectrometry 17 (14), 1611-1618 , 2003 2003 Citations: 25
Randomized clinical trial comparing the pharmacokinetics of standard-and increased-dosage lopinavir-ritonavir coformulation tablets in HIV-positive pregnant women M Santini-Oliveira, RCE Estrela, VG Veloso, VB Cattani, C Yanavich, ... Antimicrobial agents and chemotherapy 58 (5), 2884-2893 , 2014 2014 Citations: 24
Determination of didanosine in human serum by on‐line solid‐phase extraction coupled to high‐performance liquid chromatography with electrospray ionization tandem mass … RCE Estrela, MC Salvadori, RSL Raices, G Suarez‐Kurtz Journal of mass spectrometry 38 (4), 378-385 , 2003 2003 Citations: 23
Prednisolone: limited sampling strategies for estimating pharmacokinetic parameters G Suarez-Kurtz, EE Rita de Cássia, MC Salvadori Therapeutic drug monitoring 26 (1), 16-22 , 2004 2004 Citations: 19
Limited penetration of lopinavir and ritonavir in the genital tract of men infected with HIV-1 in Brazil TRC Vergara, RCE Estrela, G Suarez-Kurtz, M Schechter, J Cerbino-Neto, ... Therapeutic drug monitoring 28 (2), 175-179 , 2006 2006 Citations: 17
Disulfiram repurposing in the combined chemotherapy of Chagas disease: A protocol for phase I/II clinical trial RM Saraiva, LF Portela, GPE da Silveira, NL da Silva Gomes, DP Pinto, ... Medicine: Case Reports and Study Protocols 2 (7), e0110 , 2021 2021 Citations: 16
Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: a nested drug–drug interaction study in a cohort of Brazilian transgender women … RE Vitória Berg Cattani, Emilia Moreira Jalil, Leonardo Eksterman, Thiago ... Journal of Antimicrobial Chemotherapy 77 (10), 2729–2736 , 2022 2022 Citations: 13
Implementation of vancomycin dosing nomogram in an electronic prescribing system: an innovative tool in antibiotic stewardship TM Lima, SC Elias, RCE Estrela, FLL Cardoso Brazilian Journal of Pharmaceutical Sciences 50 (3), 567-572 , 2014 2014 Citations: 11
