A5070451566- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Pharmaceutical studies and practices
- Drug Transport and Resistance Mechanisms
- Pancreatic function and diabetes
- Pharmacogenetics and Drug Metabolism
- Statistical Methods in Clinical Trials
- Chronic Lymphocytic Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Diabetes Management and Research
- Biotin and Related Studies
- Chronic Kidney Disease and Diabetes
- Neuroendocrine Tumor Research Advances
- Gastric Cancer Management and Outcomes
- Helicobacter pylori-related gastroenterology studies
- Analytical Methods in Pharmaceuticals
- Blood Pressure and Hypertension Studies
- Blood Coagulation and Thrombosis Mechanisms
- Plant-based Medicinal Research
- Drug Solubulity and Delivery Systems
- Pharmacology and Obesity Treatment
- HIV/AIDS drug development and treatment
- Child and Adolescent Psychosocial and Emotional Development
- Smoking Behavior and Cessation
- Computational Drug Discovery Methods
Pfizer (United States)
2010-2025
John Wiley & Sons (United States)
2019
University of Florida
2017
Columbus Oncology and Hematology Associates
2017
Bristol-Myers Squibb (Sweden)
2009
Abstract Background Accumulating evidence supports the role of mineralocorticoid receptor (MR) in pathogenesis diabetic nephropathy. These findings have generated renewed interest novel MR antagonists with improved selectivity against other nuclear hormone receptors and a potentially reduced risk hyperkalemia. Characterization warrants establishing translatable biomarkers activity at receptor. We assessed translatability urinary sodium to potassium ratio (Na + /K ) plasma aldosterone as...
Abstract Ertugliflozin is a highly selective and potent inhibitor of the sodium‐glucose cotransporter 2 in development for treatment type diabetes mellitus. The glycemic efficacy inhibitors such as ertugliflozin depends on glucose filtration through kidney. This phase 1, open‐label study evaluated effect renal impairment pharmacokinetics, pharmacodynamics, tolerability (15 mg) mellitus healthy subjects with normal function (estimated glomerular rate not normalized body surface area ≥90...
Over the last 3 decades, there has been little change in paradigm to derive dosing recommendations for specific populations (e.g., renal failure, elderly, or obese patients) despite better understanding of clearance pathways these groups and availability modeling simulation tools. Dosing are often incomplete unavailable at time drug approval. Currently, is no regulatory framework incorporate model-based populations. This paper proposes a scientific using support population recommendations....
PBPK models are gaining special interest as a drug development tool to estimate the effect of intrinsic and extrinsic factors on pharmacokinetics. The IQ Consortium Clinical Pharmacology Organ Impairment Working Group conducted survey across member pharmaceutical companies understand current practices how is used in understanding hepatic impairment (HI) disposition its impact clinical development. Responses from 21 participants indicated that most organizations (~86%) already using for HI...
Model-informed drug development (MIDD) integrates data to quantify benefit/risk informing objective discovery and decisions. An additional critical benefit of MIDD is postulated be improvement in trial program efficiencies. While the application has grown, there have been no clear examples across programs demonstrate its value at portfolio level. This manuscript offers a methodology terms time cost savings. We utilized an algorithm estimate savings based on MIDD-related activities each stage...
Objectives: This study evaluated flexible-dose pharmacokinetics, safety, and effectiveness of aripiprazole in children adolescents with conduct disorder (CD). Methods: open-label, 15-day, three-center an optional 36-month extension enrolled a total 23 patients: 12 (6–12 years) 11 (13–17 CD score 2–3 on the Rating Aggression Against People and/or Property (RAAPP). Initially, protocol used following dosing: subjects <25 kg, 2 mg/day; 25–50 5 >50–70 10 >70 15 mg/day. Due to vomiting sedation,...
Drug development teams must evaluate the risk/benefit profile of new drug candidates that perpetrate drug-drug interactions (DDIs). Real-world data (RWD) can inform this decision. The purpose study was to develop a predicted impact score for DDIs perpetrated by three hypothetical via CYP3A, CYP2D6, or CYP2C9 in type 2 diabetes mellitus (T2DM), obesity, migraine. Optum Market Clarity analyzed estimate use substrates classified University Washington Interaction Database as moderate sensitive,...
Abstract Ertugliflozin, a sodium glucose cotransporter‐2 inhibitor, is approved in the United States for treatment of type 2 diabetes mellitus. A novel two‐period study design with 14 C microtracer dosing each period was used to determine absolute oral bioavailability (F) and fraction absorbed (F ) ertugliflozin. Eight healthy adult men received 100‐μg i.v. C‐ertugliflozin (400 nCi) dose 1 h after 15‐mg unlabeled ertugliflozin (period 1), followed by 100 μg orally along 15 mg 2). Unlabeled...
Ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, is approved in the United States and European Union for treatment type 2 diabetes adults, both as monotherapy part fixed-dose combination (FDC) therapies with either sitagliptin or immediate-release metformin. The effect a standard, high-fat breakfast on pharmacokinetics highest strengths ertugliflozin (15 mg), ertugliflozin/sitagliptin FDC (15-/100-mg), ertugliflozin/metformin (7.5-/1000-mg) tablets was evaluated. In 3 separate...
Abstract Ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor for the treatment of adults with type diabetes mellitus, is expected to be coadministered sitagliptin, metformin, glimepiride, and/or simvastatin. Four separate open‐label, randomized, single‐dose, crossover studies were conducted in healthy assess potential pharmacokinetic interactions between ertugliflozin 15 mg and sitagliptin 100 (n = 12), metformin 1000 18), glimepiride 1 or simvastatin 40 18). Noncompartmental...
Abstract The recruitment of a parallel, healthy participants (HPs) arm in renal and hepatic impairment (RI HI) studies is common strategy to assess differences pharmacokinetics. Limitations this approach include the underpowered estimate exposure use drug population for which there no benefit. Recently, method was published by Purohit et. al. (2023) that leveraged prior pharmacokinetic (PopPK) modeling-based simulation infer distribution ratios between RI/HI arms HPs. successful, but it...
Abstract Dose recommendations for specific populations are not always provided and, when available, typically rely on empirical derivation from a small fraction of the general population. In this study, prediction/confirmation framework was applied to 2 model‐based methods, physiologically based pharmacokinetics (PBPK) and static model, evaluate their ability predict clearance in mild, moderate, severe renal impairment inform dosing these populations. Simulated impairment/healthy subject AUC...
Abstract Ertugliflozin, a selective sodium‐glucose cotransporter‐2 inhibitor, is being developed for the treatment of type 2 diabetes mellitus. This randomized, 6‐sequence, 3‐period crossover study assessed effect ertugliflozin (100 mg; supratherapeutic dose) vs placebo and moxifloxacin (400 positive control) on QT interval corrected heart rate (QTc) in 42 male or female healthy subjects. Triplicate electrocardiograms were performed predose serially over 48 hours postdose each period. The...
Ertugliflozin is approved in the US and European Union as a stand-alone product for adults with type 2 diabetes mellitus once daily (QD) dosing. The fixed-dose combination (FDC) of ertugliflozin immediate-release metformin dosed twice (BID). This study assessed steady-state pharmacokinetics (PK; area under concentration-time curve over 24 hours (AUC
To assess drug-drug interaction (DDI) of zavegepant with rifampin and other medications using physiologically-based pharmacokinetic (PBPK) modeling.