Mailland F, Groothold G, Poli A, Pantarotto C
Methods Find Exp Clin Pharmacol. 1986 Sep;8(9):567-74.
A kinetic model has been employed to compare the duration of the antihypertensive activity of indenolol to its plasma half-life both after single administration and at steady-state. After a 14 day run-in period with placebo, 60 or 120 mg indenolol were given to hypertensive patients I or II grade, according to W.H.O. guidelines, once a day for 14 days. Blood samples were drawn and blood pressure recorded at intervals after the first dose, during treatment and after the last dose of the compound. Both plasma concentration and mean arterial pressure difference curves were fitted by a first order input-output model, where plasma half-life was 4 h, while pharmacological half-life was 24 h for both dose-levels tested. Therefore, with once-a-day dose regimen an accumulation of the antihypertensive effect of indenolol was demonstrated, with 99% steady-state of blood pressure reached after 7 days, while the drug did not accumulate in the central compartment.
已采用动力学模型比较了茚诺洛尔单次给药后及稳态时其降压活性持续时间与其血浆半衰期的关系。在使用安慰剂进行14天的导入期后，根据世界卫生组织指南，给I级或II级高血压患者每天服用一次60或120毫克茚诺洛尔，持续14天。在首次给药后、治疗期间及最后一剂化合物给药后，定期采集血样并记录血压。血浆浓度和平均动脉压差曲线均用一级输入-输出模型拟合，其中血浆半衰期为4小时，而所测试的两个剂量水平的药理半衰期均为24小时。因此，采用每日一次的给药方案时，茚诺洛尔的降压作用会出现蓄积，7天后血压达到99%的稳态，而该药物在中央室中不会蓄积。
