Ensing K, in 't Hout W G, Halma P, Klinkers H M, Ensing G J, de Zeeuw R A
Department of Toxicology, State University, Groningen, The Netherlands.
Arzneimittelforschung. 1988 Jan;38(1):106-11.
6 beta,7 beta-Epoxy-3a(1aH,5aH)-tropanyl-(S)-tropate (scopolamine) has proved to be a very effective drug in the prevention of motion sickness, however, the drug has a small therapeutic window, a low bioavailability and a short half-life. A transdermal drug delivery system (Scopoderm TTS) was developed to circumvent these problems as well as the variability in gastric absorption. In order to study the pharmacokinetics of the drug and its glucuronide, a highly sensitive radioreceptor assay with an absolute detection limit of 15 pg scopolamine was developed. In children undergoing minor surgery, a Scopoderm TTS patch of different sizes (according to the age of the children) was applied to the retro-auricular skin. Urine samples were collected and assayed for free and conjugated scopolamine. Furthermore possible anticholinergic effects on the pupil reaction, salivation, blood pressure and heart rate were monitored. The urine excretion of free and glucuronidated scopolamine showed large intra- and interindividual variations. However, in all age groups relatively high percentages of free scopolamine were found, namely 47.5% (3-6 years), 48.3% (7-12 years) and 36.0% (13-18 years) of the sum of free plus glucuronidated scopolamine. During the application of the patch, a prolonged plateau of scopolamine excretion could be found. Although in general the patches were well tolerated, both locally and systematically, moderate anticholinergic effects were observed in patients.
6β,7β-环氧-3a(1aH,5aH)-托烷-(S)-托品酸酯（东莨菪碱）已被证明是预防晕动病的一种非常有效的药物，然而，该药物治疗窗窄、生物利用度低且半衰期短。为了克服这些问题以及胃吸收的变异性，研发了一种透皮给药系统（东莨菪碱透皮贴剂）。为了研究该药物及其葡糖醛酸苷的药代动力学，开发了一种绝对检测限为15 pg东莨菪碱的高灵敏度放射受体测定法。在接受小手术的儿童中，将不同尺寸（根据儿童年龄）的东莨菪碱透皮贴剂贴于耳后皮肤。收集尿液样本并测定游离和结合型东莨菪碱。此外，监测了对瞳孔反应、唾液分泌、血压和心率可能的抗胆碱能作用。游离和葡糖醛酸化东莨菪碱的尿排泄显示出较大的个体内和个体间差异。然而，在所有年龄组中均发现游离东莨菪碱的比例相对较高，即游离加葡糖醛酸化东莨菪碱总和的47.5%（3至6岁）、48.3%（7至12岁）和36.0%（13至18岁）。在贴剂应用期间，可以发现东莨菪碱排泄有一个延长的平台期。尽管一般来说贴剂在局部和全身都耐受性良好，但在患者中观察到了中度抗胆碱能作用。
