Influx and efflux of amphetamine and N-acetylamphetamine in keratinocytes, pigmented melanocytes, and nonpigmented melanocytes

Chad R. Borges, Steve D. Martin, Laurence J. Meyer, Diana G. Wilkins, Douglas E. Rollins

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

To establish an in vitro model of drug incorporation into hair and to elucidate the potential roles of hair cell selectivity and hair color in the incorporation of certain drugs into hair, the basic drug amphetamine and its nonbasic analog N-acetylamphetamine (N-AcAp) were analyzed for influx and efflux into and out of keratinocytes, pigmented melanocytes (PM), and nonpigmented melanocytes (NPM) as a model for incorporation and efflux of these drugs from hair cells. NPM were of the same melan-a cell line as PM, but cultured in the presence of the tyrosinase inhibitor phenylthiocarbamide. Results show that PM take up large amounts of the basic drug amphetamine (levels of uptake dependent on melanin content), whereas keratinocytes and NPM take up only small amounts of amphetamine. None of the cells take up N-AcAp above background levels. Interestingly, whereas keratinocytes and NPM quickly efflux most of the influxed drug, PM are slow to efflux and only efflux ∼ 65% of influxed drug, if efflux media is not refreshed. (If efflux media is periodically refreshed, PM will eventually redistribute essentially all influxed drug back into the media.) These results demonstrate that pigmented cells take up greater amounts of the basic drug amphetamine, and efflux it more slowly than nonpigmented cells. Also, these results are consistent with previous data for in vivo incorporation of amphetamine in animal hair. In combination with previous data, an overall comparison of the amphetamine and N-AcAp incorporation data support a non-diffusion mediated model for drug incorporation into hair cells.

Original languageEnglish (US)
Pages (from-to)1523-1535
Number of pages13
JournalJournal of Pharmaceutical Sciences
Volume91
Issue number6
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Keywords

  • Amphetamine
  • Color bias
  • Hair
  • Melanin

ASJC Scopus subject areas

  • Pharmaceutical Science

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