A5006375428- Tuberculosis Research and Epidemiology
- HIV/AIDS Research and Interventions
- Statistical Methods in Clinical Trials
- Mathematical Biology Tumor Growth
- Antibiotics Pharmacokinetics and Efficacy
- HIV Research and Treatment
- Pancreatic and Hepatic Oncology Research
- Mycobacterium research and diagnosis
- HIV/AIDS drug development and treatment
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Antibiotic Resistance in Bacteria
- SARS-CoV-2 and COVID-19 Research
- Antimicrobial Resistance in Staphylococcus
- Infectious Diseases and Tuberculosis
- HIV, Drug Use, Sexual Risk
- Bipolar Disorder and Treatment
- Statistical Methods and Bayesian Inference
- Organizational Strategy and Culture
- Bone health and treatments
- Pharmacogenetics and Drug Metabolism
- Cancer therapeutics and mechanisms
- Diagnosis and treatment of tuberculosis
- Biosimilars and Bioanalytical Methods
- COVID-19 Clinical Research Studies
University of California, San Francisco
2019-2025
Universidad Complutense de Madrid
2021-2025
Dali University
2024
117th Hospital of People's Liberation Army
2024
Universidad de Navarra
2016-2020
Eli Lilly (United States)
2016-2018
Eli Lilly (United Kingdom)
2016
Hydroxychloroquine (HCQ) is a promising candidate for Coronavirus disease of 2019 (COVID-19) treatment. The optimal dosing HCQ unknown. Our goal was to integrate historic and emerging pharmacological toxicity data understand safe efficacious strategies COVID-19 sources included were (i) longitudinal clinical, pharmacokinetic (PK), virologic from patients with severe acute respiratory syndrome-2 (SARS-CoV-2) infection who received or without azithromycin (n = 116), (ii) in vitro viral...
Abstract There is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and vary in treatment-shortening activity, but the molecular basis of these differences unclear, no existing assay directly quantifies ability a or regimen to shorten treatment. Here, we show historically classified as sterilizing non-sterilizing have distinct impacts on fundamental aspect Mycobacterium physiology: ribosomal RNA (rRNA) synthesis. In culture, mice, human studies,...
Linezolid is increasingly important for multidrug-resistant tuberculosis (MDR-TB) treatment. However, among children with MDR-TB, there are no linezolid pharmacokinetic data, and its adverse effects have not yet been prospectively described. We characterised the pharmacokinetics, safety, optimal dose of in treated MDR-TB.
Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on CFU of Mycobacterium in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies effect fundamental cellular process, ongoing rRNA synthesis. Here, we evaluated ability different markers to distinguish between treatments three BALB/c mouse experiments at two institutions. We confirmed that measure distinct biological...
Abstract Background Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration (TFV), however, is not fully understood. aim this study to estimate the TFV concentration. Methods Participant data from TFV-based daily oral and topical active arms phase 3 trials (iPrEx, VOICE, Partners PrEP) were pooled (n = 2950). Individual...
Abstract The missense variant, breast cancer resistance protein (BCRP) p.Q141K, which encodes a reduced function BCRP, has been linked to poor response allopurinol. Using multifaceted approach, we aimed characterize the relationship(s) between BCRP pharmacokinetics (PK) and pharmacodynamics (PD) of oxypurinol (the active metabolite allopurinol), serum uric acid (SUA) levels. A prospective clinical study (NCT02956278) was conducted in healthy volunteers were given single oral dose 300 mg...
Xenograft mice are largely used to evaluate the efficacy of oncological drugs during preclinical phases drug discovery and development. Mathematical models provide a useful tool quantitatively characterize tumor growth dynamics also optimize upcoming experiments. To best our knowledge, this is first report where unperturbed large set cell lines (n = 28) has been systematically analyzed using previously proposed model nonlinear mixed effects (NLME). Exponential was identified as governing...
In this work, a semimechanistic tumor growth-response model for gemcitabine in pancreatic (administered as single agent) and ovarian (given agent combination with carboplatin) cancer mice was developed. Tumor profiles were obtained from nude mice, previously inoculated KP4, ASPC1, MIA PACA2, PANC1 (pancreas), A2780, or SKOV3×luc (ovarian) cell lines, then treated different dosing schedules of and/or carboplatin. Data fitted using the population approach Nonlinear Mixed Effect Models 7.2....
Selenite is a radiosensitizer and inhibitor of androgen receptor expression function. In phase I study (NCT02184533) in 15 subjects with metastatic cancer receiving daily oral sodium selenite palliative radiation therapy, disease stabilization was observed, as evidenced by tumor regression, marked reduction pain symptoms, decreased prostate-specific antigen levels (only patients castrate-resistant prostate cancer). The aim this work to characterize the pharmacokinetics suggest dosing...
The aims of this study are (i) to develop a population pharmacokinetic/pharmacodynamic model daptomycin in patients with normal and impaired renal function, (ii) establish the optimal dose recommendation clinical practice. Several structural PK models including linear non-linear binding kinetics were evaluated. Monte Carlo simulations conducted fixed combination creatinine clearance (30–90 mL/min/1.73 m2) body weight (50–100 kg). final dataset included 46 157 observations. A two-compartment...
The aim of this work is to build a mechanistic multiscale pharmacokinetic model for the anticancer drug 2’,2’‐difluorodeoxycytidine (gemcitabine, dFdC), able describe concentrations dFdC metabolites in pancreatic tumor tissue dependence physiological and genetic patient characteristics, and, more general, explore capabilities limitations kind modeling strategy. A characterizing metabolic pathway (metabolic network) was developed using vitro literature data from two cancer cell lines. network...
According to the World Health Organization, number of tuberculosis (TB) infections and drug-resistant burden worldwide increased by 4.5% 3.0%, respectively, between 2020 2021. Disease severity complexity drive interest for undertaking new clinical trials provide efficient treatment limit spread drug resistance. TB Alliance conducted a phase 2 study in 106 patients guide linezolid (LZD) dose selection using early bactericidal activity over 14 days treatment. LZD is highly treatment, but...
Background/Objectives: Pathophysiological variability in patients with cancer is associated differences responses to pharmacotherapy. In this work, we aimed describe the demographic characteristics and hematological, biochemical, coagulation variables a large oncology cohort develop, optimize, provide open access modeling equations for estimation of potentially relevant pharmacokinetic modeling. Methods: Using data from 1793 cancer, divided into training (n = 1259) validation 534) datasets,...
Defining tissue and plasma‐specific prophylactic drug concentrations is central to pre‐exposure prophylaxis product development for sexual transmission of HIV‐1. Pharmacokinetic (PK) data from study RMP‐02/MTN‐006 comparing single dose oral tenofovir disoproxil fumarate with multiple rectal (TFV) gel administration in HIV‐1 seronegative adults was used construct a multicompartment plasma‐rectal population PK model TFV tenofovir‐diphosphate (TFVdp) plasma tissue. were collected five matrices:...
Appears in: EDULEARN20 Proceedings Publication year: 2020Pages: 5394-5397ISBN: 978-84-09-17979-4ISSN: 2340-1117doi: 10.21125/edulearn.2020.1420Conference name: 12th International Conference on Education and New Learning TechnologiesDates: 6-7 July, 2020Location: Online
The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. aim this analysis is to quantify the individual infection over time, using a large database high-risk (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted men who have sex with and transgender women; VOICE, young women high sexual risk; Partners PrEP, serodiscordant heterosexual couples; TDF2, BTS, persons inject drugs....
ABSTRACT Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on colony forming units of M. in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies effect fundamental cellular process: ongoing ribosomal RNA synthesis. Here we evaluated ability different markers to distinguish between treatments three BALB/c mouse experiments at two institutions. We confirmed that measure...