About

Francine Johansson Azeredo, Ph.D., is an assistant professor at the Center of Pharmacometrics & Systems Pharmacology at the University of Florida College of Pharmacy. She received her B.S. in pharmacy from the Federal University of Rio Grande do Sul in Brazil and earned her Ph.D. in Pharmaceutical Sciences at the same university under the supervision of Prof. Teresa Dalla Costa. During her Ph.D., she was a short-term scholar at Prof. Hartmut Derendorf's lab at UF, where she learned her skills in pharmacometrics. Dr. Azeredo had been an assistant professor at the Federal University of Bahia (UFBA) for almost six years, with Federal Grants. Her research projects include PK/PD modeling, microdialysis, pharmacokinetic evaluation of new compounds, and clinical population pharmacokinetics/pharmacodynamics of anti-infective drugs and drugs used to treat neglected diseases. Her research interests are in PK-PD modeling and simulation for parasitic poverty-related diseases and anti-infective agents to optimize drug therapy, focusing on combating drug-resistant Plasmodium through better information on drug-combined therapies, as well as using modeling and simulation to optimize pharmacological treatment in special populations.

Research topics

• Medicine
• Pharmacology
• Chemistry
• Biology
• Biochemistry
• Traditional medicine
• Ecology

Selected publications

• Development of a Quantitative Systems Pharmacology Model for Hepatitis B Virus Infection and Hepatitis D Virus Co-Infection.

  2026-01-01

  articleOpen access

  <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d13497e90"> <b>Objectives:</b> The Hepatitis B virus (HBV), identified as a hepatotropic, double-stranded DNA virus, gives rise to both acute and chronic diseases. HBV infection not only jeopardizes health outcomes but also results in a substantial socioeconomic burden. Therefore, the goal of our project is to establish and verify a quantitative systems pharmacology (QSP) model for HBV to characterize and predict the dynamic interplay between the virus and the patient’s immune response as well as changes therein over time. Once developed and verified, this model will be expanded to hepatitis delta virus (HDV) coinfections. Ultimately, we will use this QSP platform to inform future decision-making in the treatment and, ideally, cure of HBV and HDV. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d13497e95"> <b>Methods:</b> The acute HBV infection QSP model was implemented in MATLAB and consists of three biological compartments—liver, plasma, and lymph—representing the spatial complexity of HBV infection and immune regulation. Model structure includes over 100 biological species and simulates key processes such as viral replication, innate and adaptive immune responses, cytokine signaling, and hepatocyte turnover. Parameter values and initial conditions were derived from previously published models [ <a class="xref-link" href="#r1">1</a>– <a class="xref-link" href="#r3">3</a>], experimental literature [ <a class="xref-link" href="#r4">4</a>– <a class="xref-link" href="#r6">6</a>], and quantitative databases including CYTOCON DB and fIVE DB. Manual calibration was performed using digitized clinical data from eight acute HBV studies [ <a class="xref-link" href="#r7">7</a>– <a class="xref-link" href="#r14">14</a>] to accurately capture the time course of key biomarkers such as HBV DNA, HBsAg, and ALT. To evaluate model behavior and biological plausibility, we conducted perturbation analyses targeting immune components, local sensitivity analysis (LSA) to identify influential parameters, and generated a virtual population (VPOP) to reflect patient variability in biomarker trajectories. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d13497e119"> <b>Results:</b> The model accurately reproduced clinical dynamics of key biomarkers (HBV DNA, HBsAg, ALT), capturing hallmark phases of acute infection: peak viremia, ALT elevation during immune clearance, and biomarker resolution. Perturbation analyses underscored critical roles for CD8 ⁺ T cells, myeloid dendritic cells (mDCs), and regulatory T cells (Tregs) in determining infection fate. LSA revealed dominant influence of adaptive immune parameters and viral replication kinetics across biomarkers. The generated VPOP successfully spanned clinical variability, confirming the model’s robustness and biological relevance. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d13497e127"> <b>Conclusions:</b> This QSP model provides a mechanistic framework for simulating acute HBV infection and evaluating immune-pathogen interactions. It captures both central trends and variability in patient responses, offering a valuable tool for hypothesis testing, biomarker analysis, and treatment strategy design. Future extensions will include modeling of chronic HBV infection and HDV co-infection to support model-informed drug development (MIDD) and clinical decision-making.

  PublisherOA PDFDOI

• Pharmacokinetic and pharmacodynamic modeling of anti-plasmodial drugs mefloquine plus artesunate: insights on translational application

  Antimicrobial Agents and Chemotherapy · 2026-02-12

  articleOpen accessSenior author

  ABSTRACT A combination between artesunate (AS) and mefloquine (MQ) (ASMQ) is widely employed for the treatment of uncomplicated P. falciparum . Despite this, pharmacokinetic (PK) and underlying relationship between PK and pharmacodynamic (PD) are relatively less known than other standard combination therapy. This study aimed to develop population PK models for ASMQ combination therapy in P. berghei -infected mice and to further characterize the PK/PD relationships by assessing the impact of different dosing strategies through a model-based simulation. Plasma PK was assessed in infected mice receiving a single oral dose of 100 mg/kg AS and 55 mg/kg MQ after allometric scaling to mice dose. A two-compartment model with first-order absorption and linear elimination best described both drugs' concentration-time profiles. PK/PD modeling, performed using a turnover model in MonolixSuite 2024R1, revealed IC₅₀ values of 10.93 nM for artesunate and 29.1 nM for mefloquine, indicating strong potency. Simulations demonstrated that both ASMQ dosing regimens (100/55 and 25/55 mg/kg) resulted in comparable parasitemia suppression (~85%) and sustained efficacy. In contrast, AS monotherapy exhibited a rapid initial parasite clearance, but this was followed by a parasite recrudescence. These findings underscore the value of combination therapy and highlight the utility of integrated PK/PD modeling to inform antimalarial treatment optimization in preclinical studies and support translational application.

  PublisherDOI

• Forecasting the Biological Effect of PEGylated-rHuEPO Candidates in Chronic Kidney Disease Patients using a Middle-out Translation Approach

  Pharmaceutical Research · 2026-01-15

  article
  PublisherDOI

• Model-informed Evidence Generation to Optimize Warfarin Dosing for Hepatic Impairment

  2026-01-01

  articleOpen access

  <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d615092e114"> <b>Objectives:</b> Although warfarin is the only oral anticoagulant recommended for patients with severe hepatic impairment, specific dosing guidelines are lacking [ <a class="xref-link" href="#r1">1</a>]. This study aimed to evaluate warfarin dose adjustments in patients with liver dysfunction and different CYP2C9 and VKORC1 polymorphisms, considering the impact of reduced warfarin clearance (CL) on response, measured as the International Normalized Ratio (INR). Since warfarin is eliminated through hepatic metabolism, liver dysfunction is likely to affect drug exposure, potentially necessitating dose modifications. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d615092e122"> <b>Methods:</b> Based on a previously published population PK/PD model [ <a class="xref-link" href="#r2">2</a>], we performed simulations to evaluate warfarin dosing according to CYP2C9 and VKORC1 genotypes under 30%, 50%, and 70% reductions in CL. Simulations assessed the time required for patients to exceed the therapeutic INR range (INR &gt; 3) and compared them to those with normal hepatic functions. A 21-day treatment period was used to evaluate the need for dose adjustments based on INR responses. Simulations were performed in NONMEM v7.5 and data handling and graphics were done with R-software version 4.3.1 (www.r-project.org). <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d615092e133"> <b>Results:</b> In poor metabolizers (*2/*3, *2/*5) with VKORC1 resistance (G/G) and a 70% CL reduction, INR exceeded the therapeutic range by day 10 with a 3 mg/day dose. For 50% and 30% reductions, INR exceeded the range on days 12 and 17, respectively. However, VKORC1 sensitive (A/A) individuals maintained therapeutic INR at 1 mg/day across all CL reductions, though those with 70% reduction required closer monitoring. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d615092e138">Intermediate metabolizers (*2/*2, *1/*3, *1/*5, *1/*8) with VKORC1 resistance required a 5 mg/day dose to maintain a therapeutic INR. However, individuals with a 70% CL reduction exceeded the therapeutic range by day 10, while those with 50% and 30% reductions exceeded it by days 12 and 17, respectively. Additionally, intermediate metabolizers with VKORC1 sensitivity required a 1 mg/day dose to maintain therapeutic INR levels. Intermediate-to-normal metabolizers (*1/*2, *1/*1) with VKORC1 resistance exhibited similar patterns at 5 mg/day, with rapid excursions beyond the therapeutic range, particularly with 50% and 70% CL reductions. VKORC1 sensitive individuals showed similar trends at a 3 mg/day, exceeding the therapeutic range by day 10 in cases of 50% and 70% CL reduction. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d615092e140"> <b>Conclusions:</b> Our results indicate that patients with liver dysfunction may need dose adjustments based on their VKORC1 genotype. VKORC1 resistant patients might benefit from starting warfarin therapy at 2 mg/day, while VKORC1 sensitive patients could begin with 1 mg/day to maintain a therapeutic INR and reduce the risk of exceeding the therapeutic range. Due to the challenges in predicting hepatic impairment and the absence of validation data, further clinical studies are needed to confirm these findings.

  PublisherOA PDFDOI

• Dexamethasone in critical coronavirus disease-2019 cases: Insights from a cross-sectional study

  Journal of Clinical and Translational Research · 2025-02-05

  articleOpen accessSenior author

  Objective: The objective of the study is to describe the clinical and laboratory characteristics of critically ill coronavirus disease-2019 (COVID-19) patients treated with dexamethasone in an intensive care unit (ICU) to provide a support tool for clinical decision-making. Design: A survey was conducted among hospitalized patients from November 2020 to March 2021, with data collected through patient interviews, medical records, and laboratory tests. Setting: This is a large hospital serving as a reference center for COVID-19 care in Bahia, Brazil. Patients: A convenience sample of 22 patients admitted to the COVID-19 ICU who signed informed consent to participate in the study. Methods: A cross-sectional study of patients admitted to the ICU with COVID-19. Data were analyzed using statistical methods. Results: The most common comorbidities among patients were hypertension (54%), diabetes (36%), and cardiovascular disease (27%). Among the deaths recorded, 55% of patients had hypertension, 44% had diabetes and/or required insulin therapy, 33% had a history of cardiovascular disease (including atrial fibrillation and congestive heart failure), and 22% had a history of stroke. Renal dysfunction (elevated creatinine); liver function abnormalities (increased alanine aminotransferase and aspartate aminotransferase); and elevated levels of ferritin, fibrinogen, and D-dimer were identified as potential indicators of disease progression. Among these factors, only elevated creatinine demonstrated a statistically significant association with an increased mortality risk. Conclusion: These findings provide a better understanding of the clinical course of severe acute respiratory syndrome coronavirus 2 infections and suggest that laboratory medicine is crucial in supporting clinical decision-making and advancing scientific and healthcare knowledge during the early phases of the COVID-19 pandemic. Relevance for patients: Identifying key risk factors, such as renal dysfunction, can improve early intervention and personalized treatment for critically ill COVID-19 patients.

  PublisherDOI

• Amphotericin B tissue penetration and pharmacokinetics in healthy and Candida albicans-infected rats: insights from microdialysis and population modeling

  Frontiers in Pharmacology · 2025-01-10

  articleOpen accessSenior authorCorresponding

  Introduction This study evaluated the relationship between total plasma and free kidney concentrations of amphotericin B (AmB) in healthy and C. albicans -infected Wistar rats using microdialysis and has the potential to significantly impact future research in this field and promote the development of antifungal drugs. The findings of this study, which show that plasma levels are a good predictor for AmB kidney concentrations and can be used to optimize its dosing regimen, underscore the importance of this research. Methods Microdialysis probe recovery rates were determined by dialysis and retrodialysis in vitro , as well as by retrodialysis in vivo . The intravenous (i.v.) administration of 2.5 × 10 6 CFU/mL of C. albicans ATCC induced the infection. A 2.5 mg/kg i.v. bolus was used in healthy and C. albicans -infected rats (n = 6/group). Plasma and microdialysate samples were analyzed using HPLC-diode-array detection. AmB tissue penetration was analyzed using the ratio between the total plasma and kidney concentrations and population pharmacokinetics (PopPK) to assess the impact of the infection on the pharmacokinetic parameters. The chosen flow rate was set to 1.5 μL/min, and there was no statistical difference between the relative recovery values when changing AmB concentrations. Results and Discussion The in vivo relative recovery was determined to be 10.9% ± 3.7%. The antifungal tissue penetration was 0.77 and 0.71 for the healthy and infected animals, respectively. The structural PK model with two compartments and linear elimination describes the concentration versus time profile of AmB simultaneously in the plasma and tissue. Infection by C. albicans does not interfere with AmB kidney penetration. AmB protein binding is demonstrated to be nonlinear and dependent on the AmB concentration in the plasma of healthy and infected animals.

  PublisherOA PDFDOI

• Dexametasona em Casos Críticos de COVID-19: Insights de um Estudo Transversal e o Impacto do Acinetobacter baumannii Resistente a Carbapenêmicos em Pacientes Graves

  Revista Científica Hospital Santa Izabel · 2025-03-31

  articleOpen access

  A pandemia da COVID-19 gerou uma necessidade urgente de investigações clínicas para compreender melhor as manifestações da doença, otimizar tratamentos e mitigar riscos associados à hospitalização prolongada. Em paralelo ao enfrentamento de um novo vírus no ano de 2020, o SARS-COV-2, dois estudos surgiram na Universidade Federal da Bahia em parceria com a UTI Clínica Geral do Hospital Santa Izabel (HSI) da Santa Casa da Bahia. Uma equipe multiprofissional compôs a autoria dessa pesquisa, dentre eles médicos intensivistas, farmacêuticos, bioestatísticos e colaboradores atuantes na linha de frente dessa instituiçao de saúde. Os estudos abordaram diferentes aspectos do manejo de pacientes críticos acometidos pela COVID-19 e foram pertinentes quanto aos impactos nos desfechos clínicos e a descoberta de co-infecçoes graves.

  PublisherOA PDFDOI

• Therapeutic Drug Monitoring-Based Population Pharmacokinetics of Amikacin in Patients at a Teaching Hospital

  Antibiotics · 2025-05-22 · 1 citations

  articleOpen access

  Background: Amikacin is still an essential antimicrobial to treat life-threatening infections, including multidrug-resistant microorganisms. The effectiveness of treatment has been correlated with the Cmax/MIC ratio, with a ratio of 8 being recommended, which is difficult to reach in some patients. Appropriate antibiotic exposure is important for knowing the disposition of the drug in the population. Objectives: We aimed to integrate therapeutic drug monitoring and a populational pharmacokinetic model to assess an optimal dose regimen and respective plasma exposure. Methods: Plasma levels of amikacin in peaks and troughs were determined by LC-MS/MS. The pharmacokinetic parameter was estimated to use nonlinear mixed effect modeling in Monolix® software. The probability of target attainment was also determined using the Simulx™ software. Results: A total of 39 patients were enrolled. A one-compartment model with proportional error model best described amikacin pharmacokinetic parameters, providing a Cl of 1.49 L/h and Vc of 23.18 L. The model developed could characterize the pharmacokinetic profile in Brazilian patients who underwent therapeutic drug monitoring. Conclusions: Amikacin therapeutic drug monitoring should be associated with population pharmacokinetic analysis in dose optimization and individualization, helping maintain appropriate drug exposure in special populations such as critically ill patients. This strategy may contribute to enhancing clinical outcomes.

  PublisherOA PDFDOI

• A Quantitative Systems Pharmacology (QSP) Model of Acute Hepatitis B Virus Infection: Mechanistic Insights and Foundations for Future Extensions

  CPT Pharmacometrics & Systems Pharmacology · 2025-12-14

  articleOpen access

  ABSTRACT Chronic hepatitis B virus (HBV) infection remains a significant global health challenge. While the dynamic interplay between viral replication and host immune responses determines infection outcomes, the mechanisms driving the resolution of acute infection versus the emergence of chronicity remain incompletely understood. To address this challenge, we developed a detailed quantitative systems pharmacology (QSP) model of acute HBV infection capturing several key host immune and viral mechanisms absent in previous models. The model was parameterized using publicly available data and calibrated against clinical time‐course datasets from multiple acute HBV case studies. Perturbation and local sensitivity analyses identified key drivers of biomarker dynamics, particularly hepatitis B virus DNA (HBV DNA), hepatitis B surface antigen (HBsAg), and alanine aminotransferase (ALT). These dynamics were most sensitive to parameters governing viral replication (e.g., HBV entry via the sodium taurocholate cotransporting polypeptide [NTCP] receptor, covalently closed circular DNA [cccDNA] formation, and hepatocyte turnover) and adaptive immune responses (e.g., CD8 + T cell activity, dendritic cell–mediated priming, and regulatory T cell [Treg]–driven immunosuppression). These influential parameters were used to generate a virtual population that reproduced the observed heterogeneity in biomarker trajectories. Notably, the magnitude and timing of biomarker peaks captured most of the variability, reflecting interindividual differences in individual immune responses and viral dynamics. While the current model nicely captures processes associated with acute HBV infections, it will be extended to different stages of chronic HBV with the objective of informing the rational design of novel therapies and supporting the development of curative HBV strategies.

  PublisherOA PDFDOI

• Unravelling sources of variability on rocuronium pharmacokinetics: Implications for prolonged recovery in older patients

  British Journal of Clinical Pharmacology · 2025-01-09 · 1 citations

  articleOpen access

  AIMS: Residual neuromuscular blockade (RNB) commonly occurs when using neuromuscular blockers and increases the risk for pulmonary complications, such as airway obstruction and severe hypoxemia, in extubated patients. Rocuronium exhibits a high variability in recovery time, contributing to an increased risk for RNB. This study aimed to identify and characterize the sources of variability in rocuronium exposure and response via a population pharmacokinetic/pharmacodynamic (PK/PD) analysis and to apply the developed PK/PD model to investigate clinical implications. METHODS: A nonlinear mixed-effect model was developed for rocuronium in patients undergoing general anaesthesia, using doses of 0.3-1.2 mg/kg. Plasma concentrations and the neuromuscular block (train of four ratio) were assessed up to 6 h after dosing. The influence of age, body mass index, renal function and sex on PK and PD was explored. Simulations were performed to predict the recovery time. RESULTS: A two-compartment model with linear elimination and an indirect sigmoid I-max model was used to describe PK and PD. The transfer rate into the periphery increases with age. The predicted recovery time was significantly longer in older subjects aged 85 years (median: 2.8 h; interquartile range [IQR]: 2.18-4.0) compared to young adults aged 25 years (median: 2.5 h; IQR: 2.0-3.1) following single bolus administrations of doses ≥ 0.7 mg/kg. CONCLUSIONS: Our findings suggest that older patients take slightly longer to recover than younger adults due to an age-dependent increase in tissue uptake. However, a priori dose adjustments for rocuronium in older patients are not feasible, since age contribution is overshadowed by the overall variability in the recovery time.

  PublisherOA PDFDOI

Frequent coauthors

• Sayuri Yamashita

  Hospital Santa Izabel

  10 shared

• Teresa Dalla Costa

  Universidade Federal do Rio Grande do Sul

  8 shared

• Valdeene Vieira Santos

  Universidade Federal da Bahia

  7 shared

• Matheus Antônio da Hora Borges

  Universidade Federal da Bahia

  5 shared

• Ana Leonor Pardo Campos Godoy

  5 shared

• Elves Anderson Pires Maciel

  Hospital Santa Izabel

  5 shared

• Vera Lúcia Milani Martins

  Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Sul

  5 shared

• Natália Valadares de Moraes

  University of Florida

  4 shared

Labs

• Azeredo LabPI

Education

• Other

  University of Florida

• Ph.D.

  University of Florida