トレッドミルテスト施行時における diltiazem の薬効と体内動態に関するデータ解析

抄録

To adapt therapeutic drug monitoring to clinical practice, a pharmacokinetic and pharmacodynamic data analysis of the effects of diltiazem during treadmill tests in 22 patients with angina pectoris was performed. Scattered data obtained from the treadmill tests, pharmacokinetic parameters for diltiazem, indicators of diltiazem sensitivity, and plasma diltiazem concentrations, and effects at standard dose (60mg) were statistically analyzed, and their mutual relationships were examined by a correlation analysis and a multiple regression analysis. In addition, we derived predictive models for the effects of diltiazem from the results of the multiple regression analysis and then examined the predictive performance of these models. The patients' ages were correlated with plasma diltiazem concentrations, suggesting that plasma diltiazem concentration increases with increasing age for the same dose and after the same lapse time of following administration. On the other hand, plasma dilitiazem concentration was correlated with exercise time (Ext) at 3hr and with pressure-rate product during rest (RestPRP) at 1.5 or 3hr after administration, but not with pressure-rate product at maximum exercise (MaxPRP). The variables most correlated with Ext, RestPRP and MaxPRP were the indicators of diltiazem sensitivities calculated from the relationships between effects and plasma diltiazem concentration. An elimination rate constant (K_e) was found to affect indicators of diltiazem sensitivity during exercise, suggesting that the effects of diltiazem during exercise depend on the tissue distribution of diltiazem. The reproducibility of the predictive models derived from the multiple regression analysis was satisfactory, suggesting that these models may be useful in predicting the effects of diltiazem in individual cases by analyzing plasma diltiazem concentration data.