Roles of drug basicity, melanin binding, and cellular transport in drug incorporation into hair

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Title Roles of drug basicity, melanin binding, and cellular transport in drug incorporation into hair
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Borges, Chad Randolph
Date 2001-12
Description Hair has become a widely accepted alternative matrix for forensic drug testing. This project examined the roles of drug basicity, drug-melanin binding, and cellular transport of drugs in the phenomenon of preferential incorporation of drugs into darker versus lighter colored hair. Validated assays were developed then used to profile the melanin content in human hair of various colors. Melanin content was then correlated with codeine incorporation into the analyzed hair. Black hair from rats dosed with the basic drug amphetamine was found to contain three times the concentration of amphetamine than white hair from the same rats. In contrast, no difference in N acetylamphetamine (N-AcAp) content was found between black hair and white hair from rats dosed with N-AcAp, a nonbasic amphetamine analog. Cocaine and amphetamine, two drugs that show a hair color bias, bound to eumelanins and mixed eu-/pheomelanins to varying degrees, but not to pure pheomelanin. Benzoylecgonine (BE) and N AcAp, drugs that do not show a hair color bias, did not to bind to any subtype of melanin. Pigmented melanocytes (PM) took up large amounts of the basic drugs amphetamine and cocaine (levels of uptake dependent on melanin content), while keratinocytes and non-pigmented melanocytes (NPM) took up only small amounts of amphetamine. None of the studied cells took up N-AcAp above background levels. While keratinocytes and NPM quickly effluxed most of an influxed basic drug, PM were slow to efflux and only partially effluxed the drug, if efflux media was not refreshed. BE was quickly effluxed from both PM and NPM. Cultured cells influxed amphetamine and cocaine to far greater extents than N-AcAp and BE. This is in accord with the fact that the <italic>non-plasma-protein-bound
Type Text
Publisher University of Utah
Subject Analysis
Subject MESH Hair; Drug Toxicity; Rats; Cocaine; Amphetamines
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Roles of drug basicity, melanin binding, and cellular transport in drug incorporation into hair". Spencer S. Eccles Health Sciences Library.
Rights Management Chad Randolph Borges.
Format application/pdf
Format Medium application/pdf
Format Extent 2,919,633 bytes
Identifier undthes,4241
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Funding/Fellowship National Institutes of Health; University of Utah Graduate School
Master File Extent 2,919,682 bytes
ARK ark:/87278/s69p33ch
Setname ir_etd
ID 190588
Reference URL https://collections.lib.utah.edu/ark:/87278/s69p33ch
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