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Comparative Study | Journal Article | Research Support, Non-U.S. Gov't

In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans.

R E Dornsife, D R Averett
R E Dornsife
Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709, USA.
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D R Averett
Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709, USA.
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DOI: 10.1128/AAC.40.2.514
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ABSTRACT

Inhibition of in vitro colony formation of human hematopoietic progenitors (CFU-granulocyte-macrophage, burst-forming unit-erythroid) by the antiviral nucleoside drugs alovudine, zalcitabine, zidovudine, ganciclovir, stavudine, didanosine, lamivudine, and acyclovir was measured. Significant correlations between in vitro 50% inhibitory concentrations and the daily human exposures (area under the concentration-time curve from 0 to 24 h; in micromolar.hour) of these chronically administered drugs in human immunodeficiency virus-positive patients that induced neutropenia or anemia were demonstrated by both linear regression and Spearman rank-order analyses. These quantitative correlations allow estimation of the exposure at which bone marrow toxicity may occur with candidate compounds.

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In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans.
R E Dornsife, D R Averett
Antimicrobial Agents and Chemotherapy Feb 1996, 40 (2) 514-519; DOI: 10.1128/AAC.40.2.514

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In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans.
R E Dornsife, D R Averett
Antimicrobial Agents and Chemotherapy Feb 1996, 40 (2) 514-519; DOI: 10.1128/AAC.40.2.514
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