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Antimicrobial Agents and Chemotherapy, Feb 1996, 514-519, Vol 40, No. 2
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

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

RE Dornsife and DR Averett
Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709, USA.

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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