| Chiral analysis of d- and l-modafinil in human serum: application to human pharmacokinetic studies. | |
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MedLine Citation:
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PMID: 12657914 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Modafinil is a novel stimulant approved by the FDA for use in the management of excessive sleepiness associated with narcolepsy. Utility for other indications includes attention deficit-hyperactivity disorder (ADHD), depression, and management of cocaine dependence. To investigate the pharmacokinetics of modafinil in these patients, the authors improved and validated an HPLC method to separate and quantitate the separate enantiomers of modafinil in human serum. d- and l-Modafinil and the internal standard 3,3-diphenylpropylamine were extracted from serum, separated by gradient elution on a beta-cyclodextrin column, and then detected by UV absorbance at 225 nm. The elution gradient was developed to eliminate interferences by other drugs used to manage narcolepsy, ADHD, and stimulants of abuse, and endogenous substances in human serum. Validation studies included determination of stability, selectivity, precision, accuracy, and recovery. The method was used to investigate the pharmacokinetics of d- and l-modafinil in a volunteer after receiving 400 mg twice daily of racemic modafinil for 5 days. Interday and intraday assay variability (CV) typically ranged from 3% to 4%. The limits of detection (0.01 microg/mL) and quantitation (0.5 microg/mL) were well below the concentration expected in serum from patients receiving therapeutic doses of modafinil. The method was free from interference by methylphenidate, cocaine, commonly used antidepressants, and amphetamines. An example of apparent stereoselective disposition is presented as d-modafinil was eliminated more rapidly than l-modafinil from human serum. The validation data support the use of this method for human pharmacokinetic studies of modafinil in patients with known or suspected use of common antidepressants, psychostimulants, and drugs of abuse. |
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Authors:
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Jennifer L Donovan; Robert J Malcolm; John S Markowitz; C Lindsay DeVane |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.; Validation Studies |
Journal Detail:
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Title: Therapeutic drug monitoring Volume: 25 ISSN: 0163-4356 ISO Abbreviation: Ther Drug Monit Publication Date: 2003 Apr |
Date Detail:
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Created Date: 2003-03-26 Completed Date: 2003-08-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7909660 Medline TA: Ther Drug Monit Country: United States |
Other Details:
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Languages: eng Pagination: 197-202 Citation Subset: IM |
Affiliation:
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Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Benzhydryl Compounds
/
blood*,
chemistry,
pharmacokinetics Central Nervous System Stimulants / blood*, chemistry, pharmacokinetics Chromatography, High Pressure Liquid Cocaine / blood Cocaine-Related Disorders / metabolism Drug Interactions Drug Stability Humans Male Quality Control Stereoisomerism |
| Grant Support | |
ID/Acronym/Agency:
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M01 RR01070-18/RR/NCRR NIH HHS; N01 DA-9-8102/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzhydryl Compounds; 0/Central Nervous System Stimulants; 50-36-2/Cocaine; 68693-11-8/modafinil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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