A5009358925- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Cancer Treatment and Pharmacology
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Angiogenesis and VEGF in Cancer
- Colorectal Cancer Treatments and Studies
- HIV Research and Treatment
- Pesticide Exposure and Toxicity
- Pharmacological Effects and Toxicity Studies
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Synthesis and Biological Evaluation
- Kruppel-like factors research
- Alzheimer's disease research and treatments
- Pharmacogenetics and Drug Metabolism
- Folate and B Vitamins Research
- Gastrointestinal Tumor Research and Treatment
- Dermatology and Skin Diseases
- Metabolism and Genetic Disorders
- Neonatal Respiratory Health Research
- Adenosine and Purinergic Signaling
- Facial Rejuvenation and Surgery Techniques
- Metal complexes synthesis and properties
- Advanced machining processes and optimization
Northwestern University
2016-2023
Pfizer (United Kingdom)
2005-2008
Center for Global Development
2005
General Atomics (United States)
1999
Torrey Pines Institute For Molecular Studies
1997
Agouron Institute
1995
California Institute for Medical Research
1992
Parkinson's Foundation
1990-1992
University of California, Berkeley
1989-1990
University of California, San Francisco
1987-1989
Studies were designed to quantitatively assess the mRNA expression of 1) 10 cytochrome P450 (P450) enzymes in human cornea, iris-ciliary body (ICB), and retina/choroid relative their levels liver, 2) 21 drug transporters these tissues small intestine, or kidney. Potential species differences PEPT1, PEPT2, MDR1 also assessed ocular from rabbit, dog, monkey, human. was either absent marginal ICB, retina/choroid, suggesting a limited role for P450-mediated metabolism disposition. In contrast,...
Sunitinib is an oral multitargeted tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma, imatinib-refractory gastrointestinal stromal tumor, and pancreatic neuroendocrine tumors. The current studies were conducted to characterize pharmacokinetics, distribution, metabolism sunitinib after intravenous and/or administrations [<sup>14</sup>C]sunitinib in rats (5 mg/kg i.v., 15 p.o.), monkeys (6 humans (50 mg p.o.). After administration, plasma concentration total...
The recently introduced Clonetics human corneal epithelium (cHCE) cell line is considered a promising in vitro permeability model, replacing excised animal cornea to predict of topically administered compounds. purpose this study was further characterize cHCE as model from both drug metabolism and transport aspects. First, good correlation found the values (P(app)) obtained rabbit corneas for various ophthalmic drugs markers. Second, previously established real-time quantitative polymerase...
Astrocytes are likely to be a main locus for the metabolic bioactivation of neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, detailed analysis MPTP metabolism was conducted in primary cultures mouse astrocytes. A constant rate conversion 1.22 nmol/mg protein per hr observed when astrocyte were incubated presence 250 microM 4 days. Three metabolites detected as products conversion: 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPDP+),...
The conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to its toxic 1-methyl-4-phenylpyridinium (MPP+) metabolite catalyzed by monoamine oxidase (MAO) type B is likely occur within glial cells in the central nervous system. In this study, primary cultures mouse astrocytes were used assess biochemical and consequences exposure MPTP. MPTP caused a concentration-dependent loss cell viability. This effect was probably due intracellular generation MPP+, because cytotoxicity...
Abstract Dopaminergic neurons are a primary target for 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) neurotoxicity. However, the conversion of MPTP to its neurotoxic 1‐methyl‐4‐phenylpyridinium metabolite (MPP+) is likely occur in astrocytes via monoamine oxidase (MAO)‐dependent formation 1‐methyl‐4‐phenyl‐2,3‐dihydropyridinium intermediate (MPDP+). The main purpose this study was characterize molecular mechanism(s) by which MPP+, once generated astrocytes, may reach extracellular...
The biochemical and toxic effects of the two monoamine oxidase-generated metabolites 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were investigated using primary cultures mouse astrocytes. After addition equimolar concentrations (25 microM) these metabolites, namely 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+) ion or 1-methyl-4-phenylpyridinium (MPP+) ion, similar levels MPP+ accumulated within Both MPDP+ caused cytotoxicity which was preceded by increased glucose utilization lactate...
Metabolism and disposition of capravirine, a new non-nucleoside reverse transcriptase inhibitor, were studied in healthy male volunteers who randomly divided into two groups (A B) with five subjects each group. Group A received single oral dose [<sup>14</sup>C]capravirine (1400 mg) group B multiple doses ritonavir (100 mg), followed by mg). Mean total recoveries radioactivity for 86.3% 79.0%, respectively, mean cumulative recovery urine comparable that feces both groups. Excretion unchanged...
Capravirine, a non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1, undergoes extensive oxygenations to numerous sequential metabolites in humans. Because several possible oxygenation pathways may be involved formation and/or metabolism single metabolite, it is very difficult or even impossible determine definitive and their relative contributions overall capravirine using conventional approaches. For this reason, liver microsome-based...
Capravirine, a new non-nucleoside reverse transcriptase inhibitor, undergoes extensive oxygenation reactions, including <i>N</i>-oxidation, sulfoxidation, sulfonation, and hydroxylation in humans. Numerous primary (mono-oxygenated) sequential (di-, tri-, tetraoxygenated) metabolites of capravirine are formed via the individual or combined pathways. In this study, cytochrome P450 enzymes responsible for reactions human liver microsomes were identified at specific pathway level. The total is...