A5061341188- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Pregnancy and Medication Impact
- Birth, Development, and Health
- Drug Transport and Resistance Mechanisms
- Maternal Mental Health During Pregnancy and Postpartum
- Neonatal Respiratory Health Research
- Maternal and Perinatal Health Interventions
- Pharmacovigilance and Adverse Drug Reactions
- Biomedical Text Mining and Ontologies
- Pharmacological Effects and Toxicity Studies
- Prenatal Substance Exposure Effects
- Pregnancy and preeclampsia studies
- Reproductive Health and Contraception
- Bariatric Surgery and Outcomes
- Opioid Use Disorder Treatment
- Statistical Methods in Clinical Trials
- Gestational Diabetes Research and Management
- Maternal and fetal healthcare
- Cancer Treatment and Pharmacology
- Alzheimer's disease research and treatments
- Pharmaceutical studies and practices
- Preterm Birth and Chorioamnionitis
- Chronic Kidney Disease and Diabetes
Indiana University – Purdue University Indianapolis
2016-2025
Indiana University School of Medicine
2016-2025
Indiana University
2015-2025
University School
2015-2025
Indiana University Health
2023-2025
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
2025
Purdue University West Lafayette
2025
American College of Clinical Pharmacy
2023
University of North Carolina at Pembroke
2023
Iowa City Public Library
2023
Abstract Background This study evaluates the relationship between cytochrome P450 (CYP) 3A5 genotype and vincristine‐induced peripheral neuropathy (VIPN) in children with precursor B cell acute lymphoblastic leukemia (preB ALL). We have shown vitro that vincristine is metabolized significantly more efficiently by CYP3A5 than CYP3A4. also found neurotoxicity less common African‐Americans (70% express CYP3A5) Caucasians. test hypothesis expressers experience do non‐expressers. Procedure of...
Capecitabine is an oral prodrug of 5-fluorouracil that indicated for the treatment breast and colorectal cancers. A three-step in vivo-targeted activation process requiring carboxylesterases, cytidine deaminase, thymidine phosphorylase converts capecitabine to 5-fluorouracil. Carboxylesterases hydrolyze capecitabine's carbamate side chain form 5'-deoxy-5-fluorocytidine (5'-DFCR). This study examines steady-state kinetics recombinant human carboxylesterase isozymes (CES) 1A1, CES2, CES3...
Drug-drug interactions (DDIs) are a common cause of adverse drug events. In this paper, we combined literature discovery approach with analysis large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set 13197 potential DDIs based on substrates inhibitors cytochrome P450 (CYP) metabolism enzymes identified from published in vitro pharmacology experiments. Using clinical repository over 800,000 patients, narrowed theoretical 3670 pairs...
AP endonuclease-1/Redox factor-1 (APE1/Ref-1 or Ref-1) is a multifunctional protein that overexpressed in most aggressive cancers and impacts various cancer cell signaling pathways. Ref-1's redox activity plays significant role activating transcription factors (TFs) such as NFκB, HIF1α, STAT3 AP-1, which are crucial contributors to the development of tumors metastatic growth. Therefore, potent, selective inhibitors target Ref-1 function an appealing approach for therapeutic intervention. A...
Carboxylesterases metabolize ester, thioester, carbamate, and amide compounds to more soluble acid, alcohol, amine products. They belong a multigene family with about 50% sequence identity between classes. CES1A1 CES2 are the most studied human isoenzymes from class 1 2, respectively. In this study, we report cloning expression of new isoenzyme, CES3, that belongs 3. The purified recombinant CES3 protein has carboxylesterase activity. carbamate prodrug...
Prediction of the extent and time course drug-drug interactions (DDIs) between mechanism-based inhibitor diltiazem (DTZ) CYP3A4 substrate midazolam (MDZ) is confounded by time- concentration-dependent clearance inhibitor. Semiphysiologically based pharmacokinetic (PBPK) models were developed for DTZ MDZ with major metabolite DTZ, <i>N-</i>desmethyldiltiazem (nd-DTZ), incorporated in model. Enzyme kinetic parameters (<i>k</i><sub>inact</sub> <i>K</i><sub>I</sub>) nd-DTZ estimated vitro used...
<b><i>Background/Aims:</i></b> Identifying the best method to estimate glomerular filtration rate (GFR) in bariatric surgery patients has important implications for clinical care of obese and research into impact obesity weight reduction on kidney health. We therefore performed such an analysis before after surgical loss. <b><i>Methods:</i></b> Fasting measured GFR (mGFR) by plasma iohexol clearance was obtained 36 severely individuals....
While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety efficacy, CTs, especially phase III are costly require rigorous planning to optimize value information obtained. More effective bridging from CT was goal a September, 2018 transdisciplinary workshop....
Abstract Background Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due dose‐limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home‐based resistance training (RT) during adjuvant improves RDI patient‐reported toxicities versus usual care (UC) patients. Methods Multicenter, randomized control trial (RCT) conducted at community academic practices. Enrollment of...
The prediction of clinical drug-drug interactions (DDIs) due to mechanism-based inhibitors CYP3A is complicated when the inhibitor itself metabolized by CYP3Aas in case clarithromycin. Previous attempts predict effects clarithromycin on substrates, e.g., midazolam, failed account for nonlinear metabolism A semiphysiologically based pharmacokinetic model was developed and midazolam metabolism, incorporating hepatic intestinal non-CYP3A mechanisms. inactivation occurred at both sites....
Abstract Background Drug pharmacokinetics parameters, drug interaction and pharmacogenetics data have been unevenly collected in different databases published extensively the literature. Without appropriate ontology a well annotated corpus, it will be difficult to develop text mining tools for collection from literature integration multiple databases. Description A comprehensive was constructed. It can annotate all aspects of vitro experiments vivo studies. covers metabolism transportation...
<b>Objective</b> To characterize the pharmacokinetics and pharmacogenetics of nifedipine in pregnancy. <b>Study Design</b> Pregnant women receiving oral underwent steady-state pharmacokinetic testing over one dosing interval. DNA was obtained genotyped for cytochrome P450 (CYP) <i>3A5</i> <i>CYP3A4*1B</i>. Nifedipine oxidized concentrations were measured plasma, parameters compared between those who expressed a <i>CYP3A5*1</i> allele only variant <i>CYP3A5</i> alleles (<i>*3</i>,<i>*6</i>,...
This study's primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral GDM receiving either monotherapy (n = 24) or a combination glyburide 30) as well type 2 (T2DM) were determined utilizing noncompartmental techniques. Maternal and umbilical cord blood samples collected at delivery from 38 women. With both 500- 1000-mg doses, bioavailability, volume distribution...
Abstract Introduction Preclinical testing in animal models is a critical component of the drug discovery and development process. While hundreds interventions have demonstrated preclinical efficacy for ameliorating cognitive impairments models, none confirmed Alzheimer's disease (AD) clinical trials. Critically this lack translation to clinic points part issues with assays used, scientific rigor reproducibility during execution. In an effort improve translation, Testing Core (PTC) Model...
Enhanced Recovery After Surgery (ERAS) protocols for cesarean deliveries (CDs) utilize multimodal pain management strategies that often include gabapentin. While gabapentin is excreted in breast milk, its pharmacokinetics immediately postpartum lactating women are not known. This observational pharmacokinetic study (NCT05099484) enrolled 21 healthy singleton pregnant individuals, ≥ 18 years old, undergoing CD and planning to breastfeed. Participants received 300 mg oral before every 6 h 48...
Objectives: : Over the last twenty years, there has been a growing utilization of different in vitro models within pharmaceutical sector to examine absorption, distribution, metabolism, and excretion (ADME) processes. This surge can be attributed significant role that poor ADME properties play, accounting for 40% drug candidate setbacks during clinical phase development]In quest develop effective treatments Alzheimer's Disease (AD), series novel compounds targeting PLCG2 were evaluated using...
Background – Enoxaparin is an anticoagulant used for preventing and treating venous thromboembolism. However, there limited information on optimal enoxaparin dosing absence of evidence-based dosage regimens in neonates infants, especially critically ill patients. This project aims to develop a population pharmacokinetic model describe the anti-factor Xa (anti-Xa) activity-time profile identify sources variation anti-Xa activity following subcutaneous administration infants.Method Anti-Xa...
Objectives: Caffeine is extensively used in neonatal intensive care units (NICUs) to treat and prevent bronchopulmonary dysplasia (BPD) neurodevelopmental insufficiency (NDI) premature infants. It effectively reduces the duration of respiratory assistance needed by stimulating spontaneous breathing through adenosine antagonism. Moderate caffeine consumption (less than 200 mg per day) during pregnancy does not appear be a major contributing factor miscarriage or preterm birth [1]. Currently,...