A5027176303- Pharmacogenetics and Drug Metabolism
- Antibiotics Pharmacokinetics and Efficacy
- Drug Transport and Resistance Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Metabolomics and Mass Spectrometry Studies
- Pharmacological Effects and Toxicity Studies
- Drug-Induced Hepatotoxicity and Protection
- Analytical Methods in Pharmaceuticals
- Anesthesia and Sedative Agents
- Antibiotic Resistance in Bacteria
- Inflammatory mediators and NSAID effects
- Diet and metabolism studies
- Dialysis and Renal Disease Management
- Pharmaceutical studies and practices
- Renal Transplantation Outcomes and Treatments
- Pharmacological Effects of Natural Compounds
- Biosimilars and Bioanalytical Methods
- Analytical Chemistry and Chromatography
- Natural Compound Pharmacology Studies
- Alcohol Consumption and Health Effects
- Herbal Medicine Research Studies
- Liver Disease Diagnosis and Treatment
- Biochemical and Molecular Research
- Central Venous Catheters and Hemodialysis
- Metabolism and Genetic Disorders
University of Florida Health Science Center
2024
University of Tennessee Health Science Center
2024
University of Florida
2012-2022
Florida College
2004-2020
Columbus Oncology and Hematology Associates
2017
Reckitt Benckiser (United States)
2017
Duke University
2014-2016
Emory University
2014-2016
University of Maryland, Baltimore
2001-2016
University of California, Davis
2014-2016
Objectives To determine whether the probe drugs caffeine, chlorzoxazone, dapsone, debrisoquin (INN, debrisoquine), and mephenytoin can be simultaneously administered as a metabolic cocktail to estimate in vivo cytochrome P450 (CYP) N-acetyltransferase enzyme activities. Methods Fourteen healthy nonsmoking male volunteers (mean age ± SD, 21.6 2.2 years) received 100 mg 250 10 debrisoquin, individually four- five-drug combinations randomized manner using 7 × Latin square. Each drug or...
Objective Imatinib is a potent inhibitor of the Bcr-Abl and c-kit tyrosine kinases approved for treatment Philadelphia chromosome–positive chronic myelogenous leukemia gastrointestinal stromal tumors. Because imatinib predominantly metabolized by cytochrome P450 (CYP) 3A4, its pharmacokinetics may be altered when it coadministered with drugs or herbs (eg, St John's wort) that modulate CYP3A4 activity. Thus we examined effects wort on pharmacokinetics. Methods This 2-period, open-label,...
Background The liver plays a significant role in drug metabolism; thus it would be expected that disease may have detrimental effect on the activity of cytochrome P450 (CYP) enzymes. extent to which presence and severity affect different individual drug-metabolizing enzymes is still not well characterized. purpose this study was assess multiple CYP by use validated cocktail approach. Methods participants investigation were 20 patients with etiologies age-, sex-, weight-matched healthy...
St. John9s wort extract (SJW) (<i>Hypericum perforatum</i> L.) is among the most commonly used herbal medications in United States. The predominance of clinical reports indicates that SJW increases activity cytochrome P450 3A4 (CYP3A4) enzyme and reduces plasma concentrations certain drugs. Although inductive effect on CYP3A4 clear, other indicate constituents may have, to a small degree, some inhibitory effects. Therefore, we sought study induction inhibition effects human hepatocyte model....
It has been postulated that carriers of PNPLA3 I148M (CG [Ile/Met] or GG [Met/Met]) develop metabolic dysfunction-associated steatotic liver disease (MASLD) in the absence insulin resistance syndrome. However, relationship between and MASLD according to
The activity of cytochrome P450 (CYP) enzymes, which determine the rate elimination lipid-soluble drugs, demonstrates considerable interindividual variability. extent to age and sex influence CYP remains unclear in humans. Our objectives were whether vivo selected enzymes is affected by or evaluate bioequivalence a large sample size.We have assessed CYP1A2, 2C19, 2D6, 2E1, 3A4 161 normal subjects (51% female 40% aged >50 years). After simultaneous administration cocktail selective probes...
ESRD can affect the pharmacokinetic disposition of drugs subject to nonrenal clearance. Cytochrome P450 (CYP) enzymes, including CYP3A, and multiple intestinal hepatic drug transporters are thought mediate this process, but extent which kidney disease alters function these proteins in humans is unknown. We used midazolam fexofenadine assess CYP3A (intestinal hepatic) transport, respectively, patients with healthy control subjects. evaluated effect uremia on transporter expression vitro by...
Antihypertensive drugs are among the most commonly prescribed for chronic disease worldwide. The response to antihypertensive varies substantially between individuals and important factors such as race that contribute this heterogeneity poorly understood. In study we use metabolomics, a global biochemical approach investigate changes induced by beta-adrenergic receptor blocker atenolol in Caucasians African Americans. Plasma from treated with was collected at baseline (untreated) after 9...
Pioglitazone is effective in improving insulin resistance and liver histology patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional mitochondrial metabolism a central feature of NASH, we hypothesized that an important target pioglitazone would be alleviating oxidative dysfunction. To this end, studied hepatic mice fed high-fructose high-transfat diet (TFD) supplemented for 20 wk, using nuclear magnetic resonance-based 13C isotopomer analysis. improved whole body adipose...
Abstract Scope: The xanthone α‐mangostin is one of the major bioactive secondary metabolites in Garcinia mangostana . Until now, vivo studies on absorption, bioavailability, disposition, and metabolism are limited. Methods results: In present study, an LC‐MS/MS assay has been established for determination rat plasma. validated method was used successfully to support pharmacokinetic rats after intravenous (i.v.) oral administration. Both non‐compartmental compartmental analyses were...
The metabolic activity of CYP2C9 in 16 subjects expressing four different genotypes (CYP2C9*1/*1, *1/*2, *1/*3, and *2/*2) was evaluated. Single oral doses tolbutamide, flurbiprofen, losartan were administered a randomized, crossover design. Plasma urine collected over 24 hours. urinary ratio amount metabolite(s) excreted correlated with formation clearance. clearance tolbutamide to its CYP2C9-mediated metabolites demonstrated stronger association genotype compared flurbiprofen losartan,...
The aim of this study was to investigate the effect commonly used botanicals on UDP-glucuronosyltransferase (UGT) 1A4, UGT1A6, and UGT1A9 activities in human liver microsomes. extracts screened were black cohosh, cranberry, echinacea, garlic, ginkgo, ginseng, milk thistle, saw palmetto, valerian addition green tea catechin epigallocatechin gallate (EGCG). Formation trifluoperazine glucuronide, serotonin mycophenolic acid phenolic glucuronide as an index reaction for UGT1A4, activities,...
Commonly used herbal supplements were screened for their potential to inhibit UGT1A1 activity using human liver microsomes. Extracts included ginseng, echinacea, black cohosh, milk thistle, garlic, valerian, saw palmetto, and green tea epigallocatechin gallate (EGCG). Estradiol-3-O-glucuronide (E-3-G) formation was as the index of activity.All extracts except garlic showed inhibition at one or more three concentrations tested. A volume per dose (VDI) calculated estimate in which daily should...
Milk thistle (Silybum marianum) extracts are widely used as a complementary and alternative treatment of various hepatic conditions host other diseases/disorders. The active constituents milk supplements believed to be the flavonolignans contained within extracts. In vitro studies have suggested that some components may significantly inhibit specific cytochrome P450 (P450) enzymes. However, determining potential for clinically significant drug interactions with products has been complicated...
Cyclophosphamide, the precursor to active 4-hydroxycyclophosphamide, is used in glomerulonephritis despite limited pharmacokinetics data. The of cyclophosphamide and 4-hydroxycyclophosphamide were evaluated. influence laboratory pharmacogenomic covariates on was evaluated as a secondary aim.Glomerulonephritis patients (n = 23) participated pharmacokinetic evaluation. Blood serially collected assayed for by LC/MS methods. Kidney function, serum albumin polymorphisms drug metabolism or...