Svedman P, Lundin S, Höglund P, Hammarlund C, Malmros C, Pantzar N
Department of Plastic and Reconstructive Surgery, Lund University, University Hospital, Malmö, Sweden.
Pharm Res. 1996 Sep;13(9):1354-9. doi: 10.1023/a:1016021900286.
To develop a clinical alternative to drug administration by injection or infusion.
A simple, mechanical device (Cellpatch) enables both the formation of a standardized small epidermal bleb and exposure of the circular base of the bleb to drug. The epidermis is split off by suctioning without bleeding or discomfort in a layer superficial to dermal capillaries and nociceptor nerves. Transdermal invasivity is thus avoided. Absorption of dextran test drug in aqueous solution vs molecular weight (3 kDa-70 kDa) and erosion area (3 kDa, diameter: 3-10 mm) were studied in healthy volunteers. The feasibility of using Morphine cellpatch (cell filled with 20 mg/ml morphine hydrochloride, aqueous solution, erosion diameter 6 mm) for post-operative pain relief was studied in two different patient groups; the Cellpatch was removed after 48 hours. Plasma morphine concentrations were determined at intervals.
Dextrans of all sizes were efficiently absorbed transdermally, although absorption decreased with increasing molecular weight. The degree of absorption was directly related to the area of the mini-erosion. There were no sign of dose-dumping even with the largest erosions. The Cellpatch performed well in the demanding conditions of the postoperative unit, and was considered easy to use. Pharmacokinetically, the postoperative morphine delivery was related to that of a continuous infusion, with variability and dose in the same range as a continuous morphine infusion used clinically for providing basal pain relief. There were no bacterial growth in the morphine cells at 48 h. Reepithelialization of the erosion was rapid.
The feasibility of administering drugs in a wide size range by passive diffusion through a standardized skin mini-erosion was demonstrated; the rate of absorption decreased with increasing molecular weight. The small area of the erosion restricts and controls the concentration driven diffusion of drug into the circulation. As a consequence of the favorable findings, three placebo-controlled clinical studies using Morphine cellpatch for postoperative pain relief are currently underway.
开发一种替代注射或输注给药的临床方法。
一种简单的机械装置（细胞贴片）能够形成标准化的小表皮水疱，并使水疱的圆形底部接触药物。通过抽吸在真皮毛细血管和伤害感受器神经上方的一层无出血或不适的浅表层分离表皮。从而避免经皮侵入性。在健康志愿者中研究了水溶液中右旋糖酐测试药物的吸收与分子量（3 kDa - 70 kDa）和侵蚀面积（3 kDa，直径：3 - 10 mm）的关系。在两个不同的患者组中研究了使用吗啡细胞贴片（填充有20 mg/ml盐酸吗啡水溶液，侵蚀直径6 mm）缓解术后疼痛的可行性；48小时后移除细胞贴片。定期测定血浆吗啡浓度。
所有大小的右旋糖酐均能有效地经皮吸收，尽管吸收随着分子量的增加而降低。吸收程度与微小侵蚀面积直接相关。即使是最大的侵蚀也没有剂量倾泻的迹象。细胞贴片在术后病房的苛刻条件下表现良好，并且被认为易于使用。从药代动力学角度看，术后吗啡给药与持续输注相关，其变异性和剂量与临床上用于提供基础疼痛缓解的持续吗啡输注在同一范围内。48小时时吗啡细胞中无细菌生长。侵蚀部位的再上皮化迅速。
证明了通过标准化的皮肤微小侵蚀进行被动扩散给药的可行性，药物大小范围广泛；吸收速率随着分子量的增加而降低。侵蚀的小面积限制并控制了药物向循环中的浓度驱动扩散。基于这些有利的研究结果，目前正在进行三项使用吗啡细胞贴片缓解术后疼痛的安慰剂对照临床研究。
