Sumner D J, Elliott H L, Reid J L
Clin Pharmacol Ther. 1982 Oct;32(4):450-8. doi: 10.1038/clpt.1982.188.
(1) When incremental infusions of drugs that increase blood pressure are given to human subjects to assess "pressor responsiveness," only the lower part of the sigmoid dose-response curve can be obtained. (2) Fitting a quadratic function does not involve discarding data points, which is usually the case with a linear fit, and it provides a more satisfactory fit to the lower part of a sigmoid dose-response curve. (3) In the presence of a competitive antagonist, a pressor dose-response curve will be shifted to the right. In this situation the dose-response curves obtained before and after treatment with antagonist should be fitted simultaneously to a quadratic model in which the parallel shift is one of the parameters. (4) The use of quadratic fitting is illustrated by reference to clinical experiments to obtain the following three curves for drugs that modify peripheral alpha adrenoceptors: norepinephrine pressor response curves after placebo and doxazosin, an alpha 1 antagonist; norepinephrine pressor response curves after placebo, labetalol, and medroxalol (drugs with combined alpha 1 and beta blocking properties); and phenylephrine pressor response curves before and after prazosin. (5) Fitting a quadratic function is the appropriate initial step in the analysis of pressor dose-response curves in man.
(1) 当向人体受试者递增输注能升高血压的药物以评估“升压反应性”时,只能获得S形剂量 - 反应曲线的较低部分。(2) 拟合二次函数并不涉及丢弃数据点,而线性拟合通常会这样做,并且它能更令人满意地拟合S形剂量 - 反应曲线的较低部分。(3) 在存在竞争性拮抗剂的情况下,升压剂量 - 反应曲线将向右移动。在这种情况下,用拮抗剂治疗前后获得的剂量 - 反应曲线应同时拟合到一个二次模型中,其中平行移动是参数之一。(4) 通过参考临床实验来说明二次拟合的应用,以获得用于调节外周α肾上腺素能受体的药物的以下三条曲线:安慰剂和α1拮抗剂多沙唑嗪后的去甲肾上腺素升压反应曲线;安慰剂、拉贝洛尔和美多心安(具有α1和β阻断特性的联合药物)后的去甲肾上腺素升压反应曲线;以及哌唑嗪前后的苯肾上腺素升压反应曲线。(5) 拟合二次函数是分析人体升压剂量 - 反应曲线的适当初始步骤。