A5071196805- Attention Deficit Hyperactivity Disorder
- Neurotransmitter Receptor Influence on Behavior
- Bipolar Disorder and Treatment
- Treatment of Major Depression
- Pharmacology and Obesity Treatment
- Analytical Chemistry and Chromatography
- Pharmacogenetics and Drug Metabolism
- Pharmaceutical studies and practices
- Hormonal Regulation and Hypertension
- Forensic Toxicology and Drug Analysis
- Metabolism and Genetic Disorders
- Cannabis and Cannabinoid Research
- Cholinesterase and Neurodegenerative Diseases
- Diet and metabolism studies
- Eicosanoids and Hypertension Pharmacology
- Analytical Methods in Pharmaceuticals
- Nitric Oxide and Endothelin Effects
- Pharmacological Effects and Toxicity Studies
- Gestational Diabetes Research and Management
- Various Chemistry Research Topics
- Prenatal Substance Exposure Effects
- Schizophrenia research and treatment
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Vitamin D Research Studies
Medical University of South Carolina
2011-2021
University of Tennessee at Knoxville
1990-2017
University of Florida
2013-2017
University of Michigan–Ann Arbor
2013-2017
University of Tennessee Health Science Center
1985-2016
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014
Ralph H. Johnson VA Medical Center
2005-2006
University of Washington
1999
University of North Carolina at Chapel Hill
1981-1991
The pharmacokinetics and bioavailability of methylphenidate (MPH) a metabolite, ritalinic acid (RA), were studied in normal adults, children with hyperactivity, monkeys rats. Adult males received 0.15 or 0.3 mg/kg MPH orally RA analyzed plasma samples obtained at various times after treatment. Maximal concentrations found to occur 2.2 hr administration either dose (range: 1.0-4.0). mean (+/-S.E.) maximal concentration for was 3.5 +/- 0.4 ng/ml 7.8 0.8 mg/kg. clearances high (10.1...
The pharmacology of the enantiomers threo-methylphenidate (MPH) was evaluated in rat to assess relative contribution each isomer central and peripheral actions racemic drug. Fractional recrystallization binaphthyl phosphate salts dl-threo-MPH allowed resolution d-threo-MPH 92% enrichment l-threo-MPH. enantiomeric disposition monitored using gas chromatographic separation trifluoroacetylprolyl diastereomeric derivatives. activity d-isomer greater than l-isomer induction locomotor inhibition...
Abstract The human hepatic microsomal vitamin D 25-hydroxylase protein and gene have not been identified with certainty. Sixteen recombinant enzymes were screened for activity; 11 had some activity, but CYP3A4 the highest activity. In characterized liver microsomes, activity correlated significantly testosterone 6β-hydroxylase Activity in pooled microsomes was inhibited by known inhibitors of an antibody to CYP3A2. Thus, is a 25-hydroxylase. Introduction: Studies performed identify D-25...
This study explores the hypotheses that: (1) ethanol will interact with dl-Methylphenidate (MPH) to enantioselectively elevate plasma d-MPH, and primarily yield l-ethylphenidate as a transesterification metabolite; (2) women exhibit lower relative bioavailability of MPH than men; (3) sex-dependent differences in subjective effects exist. dl-MPH HCl (0.3 mg/kg) was administered orally 30 min before ethanol, after (0.6 gm/kg), or without randomized, normal subject three-way crossover 10 men...
Racemic methylphenidate remains the drug of choice for attention-deficit hyperactivity disorder (ADHD). Methylphenidate appears to produce psychostimulation by inhibiting presynaptic uptake impulse-released dopamine. The absolute bioavailability in humans is quite low and variable: mean 23 per cent therapeutic (+)-isomer 5 (−)-isomer. primary site presystemic metabolism may be gut and/or intestinal wall. Brain concentrations average eight times that blood. A Tmax 1·5–2·5 h, a Cmax 6–15 ng/ml...
Milk thistle (<i>Silybum marianum</i>) extracts, one of the most widely used dietary supplements, contain a mixture six major flavonolignans (silybin A, silybin B, isosilybin silychristin, and silydianin) other components. However, pharmacokinetics free individual have been only partially investigated in humans. Furthermore, antioxidant effects extract, which may underlie basis many therapeutic effects, not thoroughly assessed. The present study evaluated healthy volunteers receiving single...
dl-Methylphenidate (MPH) has been widely used to treat attention-deficit/hyperactivity disorder (ADHD) for the last half century. It had exclusively available in racemic form, i.e., a 50:50 mixture of d- and l-isomers. However, single enantiomer formulation, d-MPH (dexmethylphenidate), became general clinical use 2002. For this reason, intrinsic pharmacological differences effects l-MPH have recently come under intense investigation. The primary therapeutic MPH are generally recognized...
Studies were performed to identify the microsomal enzyme that 24-hydroxylates vitamin D, whether 25-hydroxylation occurs, and structure function of enzyme. Sixteen hepatic recombinant cytochrome P450 enzymes expressed in baculovirus-infected insect cells screened for 24-hydroxylase activity. CYP3A4, a D-25-hydroxylase, CYP1A1 had highest activity with 1α-hydroxyvitamin D2 (1αOHD2) as substrate. The ratio rates 24-hydroxylation D3 (1αOHD3), 1αOHD2, by CYP3A4 was 3.6/2.8/1.0. Structures...
Methamphetamine abuse in young adults has long-term deleterious effects on brain function that are associated with damage to monoaminergic neurons. Administration of glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic methamphetamine animal models. Therefore, we hypothesized a partial GDNF gene deletion would increase susceptibility mice neurotoxicity during adulthood and possibly age-related deterioration behavior function. Two weeks after binge (4 ×...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and pharmacology of hydroxylated metabolites methyl phenidateKennerly S. Patrick, Clinton D. Kilts, George R. BreeseCite this: J. Med. Chem. 1981, 24, 10, 1237–1240Publication Date (Print):October 1, 1981Publication History Published online1 May 2002Published inissue 1 October 1981https://pubs.acs.org/doi/10.1021/jm00142a021https://doi.org/10.1021/jm00142a021research-articleACS PublicationsRequest reuse permissionsArticle...
Enantioselective hydrolysis of oral racemic methylphenidate (<i>dl</i>-MPH) by carboxylesterase 1 (CES1) limits the absolute bioavailability pharmacologically active <i>d-</i>MPH isomer to approximately 30% and that inactive <i>l</i>-MPH only 1–2%. Coadministration <i>dl-</i>MPH with ethanol results in elevated plasma concentrations accompanied CES1-mediated enantioselective transesterification <i>l-</i>MPH <i>l-</i>ethylphenidate (EPH). The present study tested hypothesis administration...
Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics ethylphenidate relative to major ritalinic acid, six healthy subjects who received under controlled conditions. Subjects (three males, three females) single oral dose (20 mg; 10-mg tablets) followed by consumption (0.6 g/kg) 30 min later. Methylphenidate, were quantified using liquid...
The clinical correlates of methylphenidate blood levels in hyperactive children and normal adults were examined five studies. Although occasional correlations between neuroendocrine response noted within subjects along the pharmacokinetic time profile drug, no significant associations found behavioral measures or laboratory tests attention activity. It is unlikely that routine level determinations will become a part management children.
Methylphenidate is the most commonly prescribed psychostimulant in clinical use today.Known methylphenidate metabolites include ritalinic acid, corresponding lactams, and p-hydroxymethylphenidate. Recent vitro work using rat liver preparations has indicated that ethyl ester, ethylphenidate, formed upon incubation with ethanol. This report describes first detection of ethylphenidate human blood samples obtained from two suicide victims who had overdosed on coingested Amounts detected whole...