Ishizaki T, Minegishi A, Morishita M, Odajima Y, Kanagawa S, Nagai T, Yamaguchi M
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
J Allergy Clin Immunol. 1988 Aug;82(2):146-54. doi: 10.1016/0091-6749(88)90993-1.
To explore the possibility that theophylline may act through adrenomedullary secretion of catecholamines, we examined the time courses of plasma norepinephrine (NE), epinephrine (E), and theophylline concentrations and peak expiratory flow (PEF) in nine children with an acute exacerbation of asthma receiving a 72-hour constant infusion of aminophylline. These measurements were made before (baseline) and at 2, 24, 48, and 72 hours after the infusion began. Plasma theophylline concentrations were kept constant in a near midpoint therapeutic range (mean +/- SEM, 14.1 +/- 1.3 to 16.1 +/- 1.1 micrograms/ml) during the 24- to 72-hour infusion periods. Compared with the respective baseline values (383.8 +/- 56.0 and 67.6 +/- 11.8 pg/ml for NE and E), the following postinfusion plasma catecholamines reached statistically significant difference: 664.0 +/- 125.1 pg/ml for NE at 24 hours (p less than 0.05), and 214.9 +/- 57.8, 233.7 +/- 82.2, and 137.6 +/- 39.4 pg/ml for E at 2, 24, and 48 hours (p less than 0.01). Despite the fact that similar plasma theophylline concentrations were maintained, plasma E, which peaked at 24 hours after dose, returned toward the baseline at the end of infusion (99.7 +/- 24.1 pg/ml), whereas this trend was not observed for NE. The postinfusion PEF increased (p less than 0.01) in a stepwise fashion, compared with the baseline, as the infusion progressed. The change in PEF correlated significantly (p less than 0.002) with plasma theophylline concentrations but not with the increase in plasma E from the baseline. Theophylline concentrations did not correlate with the increase in plasma NE or E from the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
为探究茶碱可能通过肾上腺髓质分泌儿茶酚胺发挥作用的可能性,我们检测了9名哮喘急性加重期儿童在接受氨茶碱72小时持续输注期间血浆去甲肾上腺素(NE)、肾上腺素(E)、茶碱浓度及呼气峰值流速(PEF)的时间进程。这些测量在输注开始前(基线)以及开始后2、24、48和72小时进行。在24至72小时的输注期间,血浆茶碱浓度维持在接近中点的治疗范围内(均值±标准误,14.1±1.3至16.1±1.1微克/毫升)。与各自的基线值(NE和E分别为383.8±56.0和67.6±11.8皮克/毫升)相比,输注后血浆儿茶酚胺出现以下具有统计学显著差异的情况:24小时时NE为664.0±125.1皮克/毫升(p<0.05),E在2、24和48小时分别为214.9±57.8、233.7±82.2和137.6±39.4皮克/毫升(p<0.01)。尽管维持了相似的血浆茶碱浓度,但给药后24小时达到峰值的血浆E在输注结束时恢复至基线水平(99.7±24.1皮克/毫升),而NE未观察到这种趋势。与基线相比,随着输注进行,输注后PEF呈逐步增加(p<0.01)。PEF的变化与血浆茶碱浓度显著相关(p<0.002),但与血浆E相对于基线的增加无关。茶碱浓度与血浆NE或E相对于基线的增加无关。(摘要截短至250字)