A5000044132- Chronic Lymphocytic Leukemia Research
- Pharmaceutical studies and practices
- Acute Myeloid Leukemia Research
- Antibiotics Pharmacokinetics and Efficacy
- Epilepsy research and treatment
- Acute Lymphoblastic Leukemia research
- Tuberculosis Research and Epidemiology
- Pharmacogenetics and Drug Metabolism
- Infectious Diseases and Tuberculosis
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Pharmacological Effects and Toxicity Studies
- Heart Failure Treatment and Management
- Health Systems, Economic Evaluations, Quality of Life
- Neonatal and fetal brain pathology
- Lung Cancer Treatments and Mutations
- Renal Transplantation Outcomes and Treatments
- Chronic Myeloid Leukemia Treatments
- Advanced Breast Cancer Therapies
- Neuroscience and Neuropharmacology Research
- Cancer Immunotherapy and Biomarkers
- Orthopedic Infections and Treatments
- Statistical Methods in Clinical Trials
- Pneumonia and Respiratory Infections
- Statistical Methods and Inference
University of Maryland, Baltimore
2015-2024
Baltimore Museum of Art
2021-2024
Manipal Academy of Higher Education
2024
Puma Biotechnology (United States)
2022-2024
SUNY Downstate Health Sciences University
2021
Center for Drug Evaluation and Research
2021
United States Food and Drug Administration
2021
University of Maryland, College Park
2019-2021
University of Florida
2019-2020
Columbus Oncology and Hematology Associates
2019-2020
To evaluate factors affecting variability in response to remimazolam general anesthesia. Plasma concentration-time data from 11 Phase 1–3 clinical trials were pooled for the population pharmacokinetic (popPK) analysis and concentration-bispectral index (BIS) 8 popPK-PD analysis. A 3-compartment model with allometric exponents on clearance volume described concentrations over time. An effect compartment an inhibitory sigmoid Emax was fit concentration-BIS data. Simulations performed assess...
Nivolumab 480 mg every 4 weeks (Q4W) is approved in the European Union, United States, and several other markets across multiple tumor types. Its approval was supported by quantitative efficacy/safety analyses bridging to 3 mg/kg 2 (Q2W).The benefit-risk profile of nivolumab Q4W relative Q2W evaluated using population pharmacokinetic modeling exposure-response (E-R) for safety efficacy. Pharmacokinetic exposures were predicted 3203 patients with melanoma, non-small-cell lung cancer (NSCLC),...
PET reveals spatially heterogeneous rifampin brain penetration, which decreases rapidly with treatment during tuberculous meningitis.
ABSTRACT Pharmacometric modeling establishes causal quantitative relationships between administered dose, tissue exposures, desired and undesired effects patient’s risk factors. These models are employed to de-risk drug development guide precision medicine decisions. However, pharmacometric tools have not been designed handle today’s heterogeneous big data complex models. We set out design a platform that facilitates domain-specific its integration with modern analytics foster innovation...
Propionic acidemia (PA) is an ultrarare disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), composed PCCA and PCCB subunits. An enzyme replacement therapy being developed using dual messenger RNA (mRNA) lipid nanoparticles (LNPs) encapsulating mRNAs encoding subunits PCC enzyme. We herein report on development a translational semimechanistic pharmacokinetic (PK) PK/pharmacodynamic (PD) model to quantify relationship between mRNA components mRNA-3927...
Objectives We present a novel framework to synthesize data sets with complex covariates, such as medical images, linked simulated longitudinal patient outcomes. This allows us evaluate and refine predictive models by providing training where true relationships are known. Our implementation focuses on generating optical coherence tomography (OCT) scans, but the is adaptable other covariates. also show that, once we have data, can model it appropriately leverage images predict Methods used...
The motivation for this work is to choose a Large Language Model (LLM) build an AI assistant scientists at PumasAI [1]. Focused on chat completion models, study investigates the effectiveness of various LLMs in facilitating pharmacometrics-related inquiries. Beyond conventional choices like GPT and Gemini [2], research explores broader spectrum LLM options [3]. This approach not only enables evaluation diverse types but also establishes framework assessing other models such as code embedding...
A prospective multicenter study was conducted to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of fludarabine plasma (f-ara-a) intracellular triphosphate (f-ara-ATP) in children undergoing hematopoietic cell transplantation (HCT) receiving with conditioning. Plasma peripheral blood mononuclear cells (PBMCs) were collected over course therapy for quantitation f-ara-a f-ara-ATP. Nonlinear mixed-effects modeling used develop PK model, including identification covariates...
Conducting and analyzing clinical trials in vulnerable neonates are extremely challenging. The aim of this analysis is to develop a morphine population pharmacokinetics (PK) model using data collected during randomized control trial with abstinence syndrome (NAS). A 3-compartment structural PK after intravenous (IV) administration from previously published work was utilized as prior, whereas an allometric scaling method physiological consideration used extrapolate profile adults pediatrics....
The severity of the ongoing opioid crisis, recently exacerbated by COVID-19 pandemic, emphasizes importance for individuals suffering from use disorder (OUD) to have access and receive efficacious, evidence-based treatments. Optimal treatment OUD should aim at blocking effects illicit opioids while controlling craving withdrawal facilitate abstinence promote recovery. present work analyses relationship between buprenorphine plasma exposure clinical efficacy in participants with moderate...
Key Points In a post hoc analysis, short-term reduction in spot urine osmolality (Uosm) was associated with decreased kidney volume growth autosomal dominant polycystic disease for both tolvaptan and instruction to increase hydration alone. For the same Uosm reduction, however, benefit greater tolvaptan, possibly because of cumulative 24-hour suppression by tolvaptan. Background addition decreasing water excretion increasing urinary concentration, antidiuretic hormone vasopressin plays role...
To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (ADHF) diuretic resistance.Retrospective cohort study.Large urban academic medical center.Adults admitted ADHF between 2005 2015 who had resistance, defined as administration IV furosemide at a dose 160 mg/day or higher (or an equivalent bumetanide), during hospitalization, then received least one (88 patients) (89 augment...
The purpose of this pilot study was to determine the pharmacokinetics and tolerability an investigational diazepam (DZP) formulation a parenteral midazolam (MDZ) following intranasal (i.n.) administration for efficient treatment seizure emergencies.Each subject received 5 mg DZP MDZ via both i.n. intravenous routes in four-way, randomized crossover trial. Blood samples were collected over 48 h. concentrations measured using HPLC. Using analog scales, subjects rated (0 = no change from...
The impact of patient-specific factors on the choice β-blocker versus calcium channel blocker therapy for rate control in emergency department (ED) patients treated atrial fibrillation (AF) was investigated.A retrospective cohort study conducted to evaluate influence demographics, prior medication use, hemodynamic and clinical characteristics, other variables selection first-line AF among admitted ED an academic medical center over a 22-month period (October 2012-July 2014) who received i.v....
Abstract Regulatory T cells (T regs ) are essential for maintaining immune homeostasis by serving as negative regulators of adaptive system effector cell responses. Reduced production or function has been implicated in several human autoimmune diseases. The cytokine interleukin 2 plays a central role promoting reg differentiation, survival, and vivo may therefore have therapeutic benefits mRNA‐6231 is an investigational, lipid nanoparticle‐encapsulated, mRNA‐based therapy that encodes...
Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form TB, are based on those developed pulmonary TB and not optimized brain penetration. Here, we perform first-in-human dynamic
Abstract Introduction: The anti-PD-1 checkpoint inhibitor NIVO provides favorable safety and efficacy when administered at 3 mg/kg Q2W across multiple tumor types. Alternative dosing schedules would provide flexibility offer benefits to patients prescribers. A well-established understanding of clinical pharmacology, robust data types well characterized, relatively flat E-R relationships for support the use model-based approaches qualify other potential doses schedules. Methods: feasibility...
A new, long-acting, subcutaneous (SC) formulation of risperidone (RBP-7000) has been developed for the treatment schizophrenia to address issues non-adherence associated with oral treatment. The objective this work was establish an exposure-response relationship between total active moiety (AM) plasma exposure (risperidone + 9-hydroxy-risperidone) and Positive Negative Syndrome Scale (PANSS) or Clinical Global Impression severity (CGI-S) scores using data from a registration trial.This Phase...
The heart exhibits the highest basal oxygen (O2) consumption per tissue mass of any organ in body and is uniquely dependent on aerobic metabolism to sustain contractile function. During acute hypoxic states, responds with a compensatory increase cardiac output that further increases myocardial O2 demand, predisposing ischemic stress dysfunction. Here, we test utility novel engineered protein derived from heme-based nitric oxide (NO)/oxygen (H-NOX) family bacterial proteins as an delivery...
We determined optimal vancomycin starting dose regimens in infants ≤180 days of age to achieve the highest probability target attainment with an area under concentration-time curve for 24 h (AUC