Schmid B, Kötter I, Heide L
Pharmazeutische Biologie, Pharmazeutisches Institut, Universität Tübingen, Germany.
Eur J Clin Pharmacol. 2001 Aug;57(5):387-91. doi: 10.1007/s002280100325.
To evaluate the pharmacokinetics of salicin and its major metabolites in humans after oral administration of a chemically standardised willow bark extract.
Willow bark extract corresponding to 240 mg salicin (1,360 mg, 838 micromol) was ingested by ten healthy volunteers in two equal doses at times 0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and its metabolites, i.e. gentisic acid and salicyluric acid, were determined using reverse-phase high-performance liquid chromatography. Renal excretion rate, elimination half-life and total bioavailability of salicylates were calculated.
Salicylic acid was the major metabolite of salicin detected in the serum (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid (4%). Peak levels were reached within less than 2 h after oral administration. Renal elimination occurred predominantly in the form of salicyluric acid. Peak serum levels of salicylic acid were on average 1.2 mg/l, and the observed area under the serum concentration time curve (AUC) of salicylic acid was equivalent to that expected from an intake of 87 mg acetylsalicylic acid.
Willow bark extract in the current therapeutic dose leads to much lower serum salicylate levels than observed after analgesic doses of synthetic salicylates. The formation of salicylic acid alone is therefore unlikely to explain analgesic or anti-rheumatic effects of willow bark.
评估口服化学标准化柳树皮提取物后,水杨苷及其主要代谢产物在人体中的药代动力学。
10名健康志愿者在0小时和3小时分两次等量摄入相当于240毫克水杨苷(1360毫克,838微摩尔)的柳树皮提取物。在24小时内,采用反相高效液相色谱法测定尿液和血清中水杨酸及其代谢产物(即龙胆酸和水杨尿酸)的水平。计算水杨酸盐的肾排泄率、消除半衰期和总生物利用度。
血清中检测到的水杨苷主要代谢产物是水杨酸(占总水杨酸盐的86%),此外还有水杨尿酸(10%)和龙胆酸(4%)。口服给药后不到2小时达到峰值水平。肾脏排泄主要以水杨尿酸的形式发生。水杨酸的血清峰值水平平均为1.2毫克/升,观察到的水杨酸血清浓度-时间曲线下面积(AUC)与摄入87毫克乙酰水杨酸预期的面积相当。
目前治疗剂量的柳树皮提取物导致的血清水杨酸盐水平远低于合成水杨酸盐镇痛剂量后观察到的水平。因此,仅水杨酸的形成不太可能解释柳树皮的镇痛或抗风湿作用。