Volz-Zang C, Eckrich B, Jahn P, Schneidrowski B, Schulte B, Palm D
Zentrum der Pharmakologie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt, Germany.
Eur J Clin Pharmacol. 1994;46(5):399-404. doi: 10.1007/BF00191900.
The effects of esmolol at different rates of infusion (100, 250 and 500 micrograms.kg-1 BW.min-1) were compared with beta-adrenoceptor occupancy (beta 1 and beta 2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 micrograms.kg-1 BW.min-1 there was a maximal beta 1-receptor occupancy of 84.7% while beta 2-receptor occupancy was below the detection limit; confirming the beta 1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 micrograms.kg-1 BW.min-1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 micrograms.ml-1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 micrograms.kg-1 BW.min-1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r = 0.97).(ABSTRACT TRUNCATED AT 250 WORDS)
比较了艾司洛尔在不同输注速率（100、250和500微克·千克⁻¹体重·分钟⁻¹）下的作用，通过亚型选择性放射受体测定法估算β肾上腺素能受体占有率（β1和β2），并用高效液相色谱法测定艾司洛尔及其酸性代谢产物的血浆浓度。在艾司洛尔输注速率高达500微克·千克⁻¹体重·分钟⁻¹时，β1受体最大占有率为84.7%，而β2受体占有率低于检测限；证实了艾司洛尔的β1选择性。运动引起的心率和收缩压升高被艾司洛尔以剂量依赖方式降低。运动期间心率和收缩压降低的输注速率估计EC50值分别为113和134微克·千克⁻¹体重·分钟⁻¹。此外，静息时心率和收缩压也有适度降低。由于艾司洛尔快速水解为其酸性代谢产物导致消除半衰期短，输注结束45分钟后可检测到高血浆浓度的代谢产物（最高80微克·毫升⁻¹），但未检测到艾司洛尔。尽管存在高血浆浓度的代谢产物，但未观察到体内效应，因此在艾司洛尔输注速率高达500微克·千克⁻¹体重·分钟⁻¹时，该代谢产物未参与观察到的效应。通过放射受体测定法检测的拮抗剂血浆浓度与通过高效液相色谱法检测的艾司洛尔血浆浓度显示出良好的相关性（r = 0.97）。（摘要截断于250字）
