消失相自動認識能力を有するＶｉｓｕａｌ ＢＡＳＩＣによるノンコンパートメント薬物動態速度論解析用プログラム“ＷｉｎＨＡＲＭＯＮＹ”の開発と評価

Abstract

A new Visual BASIC (ver. 4.0) program “WinHARMONY”, which operates withWindows 95, has been developed for the pharmacokinetic analysis of drugs. This pro gram uses the noncompartmental analysis method, where the recognition of the terminal elimination phase has an important role in the total analysis of the data. Three statistical methods for the automatic identification of the terminal elimination phase have been implemented and evaluated using two kinds of plasma drug concentrationtime data: 1) Plasma cyclosporin A (CyA) concentration-time data in 13 healthy human subjects, and 2) as an example of drugs having short and long half-lives, triazolam was selected and its plasma concentration-time data in 9 healthy human subjects under the single adminis tration and the coadministration with either ketoconazole or itraconazole were analyzed with this program. Among the three methods, an algorithm which performs an automatic identification of the terminal elimination phase based on two factors of linear regression analysis, i. e., an error variance and a confidence interval, gave the estimated value of the terminal elimination rate constant, λz, of 0.064 (mean) ±0.031 (SD) hr. This estimated value was not significantly different from the estimated value, 0.067±0.027 hr, of Grevel et al. who used a nonlinear regression analysis by assuming a two-compartment open model to describe the plasma CyA concentration-time data. Moreover, this program was found to work well even in the case of a drug with a long half-life such as triazolam under the coadministration with either ketoconazole or itraconazole. Since analytical results are shown on the CRT display and can be printed out, visual inspection of the analytical results is possible. Basically, the pharmacokinetic data are manually input and are saved at once in a data file. Prior to the analysis, each data set is read out from the data file. To improve upon a shortcoming of Visual BASIC where “DATA” command cannot be accepted, two optional data input modes are included in the program, i. e., a data file made by the format type of text file and data input by means of a spread sheet program. As this program is written in Visual BASIC, it runs on almost all personal computers except Macintosh and is thought to be useful for the analysis of pharmacokinetic data both in preclinical and clinical pharmacokinetic studies.