Dornsife R E, Averett D R
Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709, USA.
Antimicrob Agents Chemother. 1996 Feb;40(2):514-9. doi: 10.1128/AAC.40.2.514.
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.
测定了抗病毒核苷类药物阿洛维啶、扎西他滨、齐多夫定、更昔洛韦、司他夫定、去羟肌苷、拉米夫定和阿昔洛韦对人造血祖细胞（粒-巨噬细胞集落形成单位、红系爆式集落形成单位）体外集落形成的抑制作用。通过线性回归和Spearman等级分析均表明，这些长期给药的药物在导致人类免疫缺陷病毒阳性患者中性粒细胞减少或贫血时，其体外50%抑制浓度与每日人体暴露量（0至24小时浓度-时间曲线下面积；微摩尔·小时）之间存在显著相关性。这些定量相关性有助于估计候选化合物可能发生骨髓毒性的暴露量。
