Wampler G L, Carter W H, Campbell E D, Keefe P A
Department of Medicine, Richmond Veterans Administration Medical Center, Virginia 23249.
J Biopharm Stat. 1991;1(2):261-86. doi: 10.1080/10543409108835023.
A dual-exposure drug treatment of cell lines in tissue culture provides a possible method for determining schedule dependency. This is suggested by results of treatment of human small cell lung carcinoma NIH H209 and murine L1210 leukemia cell lines with cisplatin, a non-schedule-dependent drug, and etoposide, a schedule-dependent drug. Nonlinear least squares was used to estimate the dose-response surface. The estimated regression coefficients for the effect of the first dose compared to that of the second dose support the premise that cisplatin is not schedule dependent. Unlike cisplatin, the second dose of etoposide was shown to be more effective than the first dose in the human small cell carcinoma line. This agrees with known clinical results where multiple etoposide dosing has been shown to be more effective and confirms schedule dependency. This methodology, or a refinement, may offer another tool for studying schedule dependency of drugs using tissue culture methods.
在组织培养中对细胞系进行双暴露药物治疗为确定给药方案依赖性提供了一种可能的方法。用顺铂（一种非给药方案依赖性药物）和依托泊苷（一种给药方案依赖性药物）处理人小细胞肺癌NIH H209和小鼠L1210白血病细胞系的结果表明了这一点。使用非线性最小二乘法估计剂量反应曲面。与第二剂量相比，第一剂量效应的估计回归系数支持顺铂不具有给药方案依赖性这一前提。与顺铂不同，在人小细胞癌系中，第二剂量的依托泊苷比第一剂量更有效。这与已知的临床结果一致，在临床结果中已表明多次给予依托泊苷更有效，并证实了给药方案依赖性。这种方法或其改进方法可能为使用组织培养方法研究药物的给药方案依赖性提供另一种工具。
