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題名 Pharmacokinetic and Pharmacodynamic Characterization of Non-antiarrhythmic QT-Prolonging Drugs Associated With Torsades de Pointes
作者 陳桂恒;Lin, YL
Chan, K;Lin, YL
貢獻者 科管所
關鍵詞 Pharmacokinetic; Pharmacodynamic; QT prolongation; Torsades de Pointes
日期 2008
上傳時間 27-一月-2015 11:36:51 (UTC+8)
摘要 QT-prolonging drugs are occasionally associated with Torsades de Pointes (TdP). In this study, we compared the pharmacokinetic and pharmacodynamic characteristics of QT-prolonging drugs associated with TdP and those not associated with TdP. The characteristics included the enzyme responsible for QT-prolonging drug metabolism; the change in drug exposure resulting from enzyme inhibition; the elimination half-life; the volume of distribution, bioavailability and protein binding; the increase in QT interval caused by the drug; and the increase in QT interval in the presence of metabolic inhibition. The results demonstrated that 9 of the 20 selected drugs were metabolized through CYP 3A4 alone and, among them, 4 were torsadogens. In the presence of metabolic inhibition, the increases in maximum plasma concentration (Cmax) of torsadogens were not greater those of nontorsadogens. The increases in AUC, elimination half-lives, volumes of distribution, bioavailability, and protein binding were comparable between the two groups. Almost all torsadogens caused an increase in QT interval greater than 10 msec. In contrast, only one nontorsadogen did. With concomitant administration of enzyme inhibitors, torsadogens caused an increase in QT interval ranging between 30 msec and 82 msec, while those of nontorsadogens were up to a maximum of 16 msec. In conclusion, drugs metabolized through CYP 3A4 alone are not necessarily more likely to be proarrhythmic. The increases in QT interval induced by the torsadogens are slightly greater than those of nontorsadogens. With metabolic inhibition, they are associated with significantly greater increases in QT interval.
關聯 Drug Info. Journal, 42(3), 211-219
10.1177/009286150804200302
資料類型 article
dc.contributor 科管所
dc.creator (作者) 陳桂恒;Lin, YLzh_TW
dc.creator (作者) Chan, K;Lin, YL
dc.date (日期) 2008
dc.date.accessioned 27-一月-2015 11:36:51 (UTC+8)-
dc.date.available 27-一月-2015 11:36:51 (UTC+8)-
dc.date.issued (上傳時間) 27-一月-2015 11:36:51 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/73170-
dc.description.abstract (摘要) QT-prolonging drugs are occasionally associated with Torsades de Pointes (TdP). In this study, we compared the pharmacokinetic and pharmacodynamic characteristics of QT-prolonging drugs associated with TdP and those not associated with TdP. The characteristics included the enzyme responsible for QT-prolonging drug metabolism; the change in drug exposure resulting from enzyme inhibition; the elimination half-life; the volume of distribution, bioavailability and protein binding; the increase in QT interval caused by the drug; and the increase in QT interval in the presence of metabolic inhibition. The results demonstrated that 9 of the 20 selected drugs were metabolized through CYP 3A4 alone and, among them, 4 were torsadogens. In the presence of metabolic inhibition, the increases in maximum plasma concentration (Cmax) of torsadogens were not greater those of nontorsadogens. The increases in AUC, elimination half-lives, volumes of distribution, bioavailability, and protein binding were comparable between the two groups. Almost all torsadogens caused an increase in QT interval greater than 10 msec. In contrast, only one nontorsadogen did. With concomitant administration of enzyme inhibitors, torsadogens caused an increase in QT interval ranging between 30 msec and 82 msec, while those of nontorsadogens were up to a maximum of 16 msec. In conclusion, drugs metabolized through CYP 3A4 alone are not necessarily more likely to be proarrhythmic. The increases in QT interval induced by the torsadogens are slightly greater than those of nontorsadogens. With metabolic inhibition, they are associated with significantly greater increases in QT interval.
dc.format.extent 10289841 bytes-
dc.format.mimetype application/pdf-
dc.relation (關聯) Drug Info. Journal, 42(3), 211-219
dc.relation (關聯) 10.1177/009286150804200302
dc.subject (關鍵詞) Pharmacokinetic; Pharmacodynamic; QT prolongation; Torsades de Pointes
dc.title (題名) Pharmacokinetic and Pharmacodynamic Characterization of Non-antiarrhythmic QT-Prolonging Drugs Associated With Torsades de Pointes
dc.type (資料類型) articleen