Higenamine is a β₂-agonist that has been prohibited in sports by the World Anti-Doping Agency. Higenamine could potentially promote anabolism and lipolysis; however, its crucial pharmacokinetics data, particularly muscle distribution, remain unavailable. The present study aims to investigate the blood-to-muscle distribution as well as the urinary excretion of higenamine in laboratory rats. In the first experiment, the microdialysis technique was employed to continuously measure free, protein-unbound concentrations in blood and muscle for 90 min (sampling at a 5-min interval) after rats received IV infusion of higenamine. The mean half-lives of higenamine in blood and muscle were 17.9 and 19.0 min, respectively. The blood-to-muscle distribution ratio (AUC_muscle/AUC_blood) of higenamine was estimated to be 22%. In the second experiment, rats were orally administered with a single-dose higenamine, and their urine samples were profiled at a 12-h interval for up to 48 h. Results showed only a small portion of total consumption (1.44%, ranging 0.71%–2.50%) was excreted in the urine. Among these time points, about 43% cumulative amount of higenamine was eliminated within the first 12 h. Our data suggested that one-quarter of the unbound higenamine rapidly penetrates from the vessels into muscle, distributes to the interstitial fluid, then eliminates from the rat in a short span of time. The muscle tissue is likely to have a low binding affinity for higenamine, and renal excretion plays a minor role in its elimination. Together, our findings provide valuable pharmacokinetics data that may gain deeper insights into higenamine's role in skeletal muscle functions.

中文翻译：

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大鼠去甲素的血液-肌肉分布和尿排泄

Higenamine 是一种 β ₂ -激动剂，已被世界反兴奋剂机构禁止用于体育运动。Higenamine 可能会促进合成代谢和脂肪分解；然而，它的关键药代动力学数据，特别是肌肉分布，仍然无法获得。本研究旨在调查实验室大鼠中去甲肾上腺素的血液-肌肉分布以及尿液排泄。在第一个实验中，在大鼠接受静脉输注去甲酚胺后，采用微透析技术连续测量血液和肌肉中游离的、未结合蛋白质的浓度 90 分钟（以 5 分钟间隔取样）。去甲叶黄素在血液和肌肉中的平均半衰期分别为 17.9 和 19.0 分钟。血液与肌肉的分布比（AUC_肌肉/AUC_血液) 的去甲素胺估计为 22%。在第二个实验中，大鼠口服单剂量去甲乌药，并以 12 小时的间隔对它们的尿液样本进行分析，最长可达 48 小时。结果显示，总消耗量中只有一小部分（1.44%，范围为 0.71%–2.50%）从尿液中排出。在这些时间点中，在前 12 小时内消除了约 43% 累积量的去甲乌药碱。我们的数据表明，四分之一的未结合去甲肾上腺素胺迅速从血管渗透到肌肉中，分布到间质液中，然后在短时间内从大鼠体内消除。肌肉组织可能对去甲酚胺的结合亲和力较低，肾脏排泄在其消除中起次要作用。一起，