Reid J L, Barber N D, Davies D S
Arch Int Pharmacodyn Ther. 1980;Suppl:11-6.
The clinical pharmacology of clonidine has been studied using a sensitive specific method of drug analysis and quantitative measures of cardiovascular and other drug effects. The plasma concentration effect relationship for dry mouth and sedation is log linear until a maximum effect is achieved. The relationship of plasma level to hypotensive effect in man and animals shows a positive correlation over a narrow concentration range up to 1.5--2.0 ng/ml. At higher plasma levels a reversal of hypotension occurs with hypertension at concentrations over 10 ng/ml. This "therapeutic window" may reflect actions of clonidine on alpha receptors in the brain stem which lower blood pressure counteracted by peripheral effects of vascular alpha receptors which causes hypertension. Information on the pharmacokinetics and dynamics of clonidine can assist in optimising this form of antihypertensive therapy.
已采用灵敏、特异的药物分析方法以及心血管和其他药物效应的定量测定方法对可乐定的临床药理学进行了研究。口干和镇静作用的血浆浓度效应关系呈对数线性，直至达到最大效应。在人和动物中，血浆水平与降压作用的关系在高达1.5 - 2.0 ng/ml的狭窄浓度范围内呈正相关。在较高血浆水平时，当浓度超过10 ng/ml时，会出现低血压逆转并伴有高血压。这个“治疗窗”可能反映了可乐定对脑干α受体的作用，该作用降低血压，但被血管α受体的外周效应抵消，后者导致高血压。关于可乐定药代动力学和药效学的信息有助于优化这种抗高血压治疗方式。
