Zecca Ernesto, Manzoni Andrea, Centurioni Fabio, Farina Alberto, Bonizzoni Erminio, Seiler Dan, Perrone Tania, Caraceni Augusto
Palliative Care, Pain Therapy and Rehabilitation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Medical Affairs Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy.
Br J Clin Pharmacol. 2015 Jul;80(1):110-5. doi: 10.1111/bcp.12595. Epub 2015 May 28.
Transdermal fentanyl is a well established treatment for cancer pain. The aim of the present study is to assess the relative bioavailability of fentanyl from two different transdermal systems by evaluating plasma drug concentrations after single administration of Fentalgon® (test), a novel bilayer matrix type patch, and Durogesic SMAT (reference), a monolayer matrix type patch. In the Fentalgon patch the upper 6% fentanyl reservoir layer maintains a stable concentration gradient between the lower 4% donor layer and the skin. The system provides a constant drug delivery over 72 h.
This was an open label, single centre, randomized, single dose, two period crossover clinical trial, that included 36 healthy male volunteers. The patches were applied to non-irritated and non-irradiated skin on the intraclavicular pectoral area. Blood samples were collected at different time points (from baseline to 120 h post-removal of the devices) and fentanyl concentrations were determined using a validated LC/MS/MS method. Bioequivalence was to be claimed if the 90% confidence interval of AUC(0,t) and C(max) ratios (test: reference) were within the acceptance range of 80-125% and 75-133%, respectively.
The 90% confidence intervals of the AUC(0,t) ratio (116.3% [109.6, 123.4%]) and C(max) ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the C(max) ratio also met the narrower bounds of 80-125%. There was no relevant difference in overall safety profiles of the two preparations investigated, which were adequately tolerated, as expected for opioid-naïve subjects.
The new bilayer matrix type patch, Fentalgon®, is bioequivalent to the monolayer matrix type Durogesic SMAT fentanyl patch with respect to the rate and extent of exposure of fentanyl (Eudra/CT no. 2005-000046-36).
透皮芬太尼是一种成熟的癌症疼痛治疗方法。本研究的目的是通过评估单次给予新型双层基质型贴片Fentalgon®（试验品）和单层基质型贴片多瑞吉SMAT（参比品）后血浆药物浓度，来评估两种不同透皮给药系统中芬太尼的相对生物利用度。在Fentalgon贴片中，上层6%的芬太尼储库层在下层4%的供体层和皮肤之间维持稳定的浓度梯度。该系统可在72小时内持续给药。
这是一项开放标签、单中心、随机、单剂量、两期交叉临床试验，纳入了36名健康男性志愿者。将贴片贴于锁骨内胸区域未受刺激和未受辐照的皮肤上。在不同时间点（从基线到移除装置后120小时）采集血样，并使用经过验证的液相色谱/串联质谱法测定芬太尼浓度。如果AUC(0,t)和C(max)比值（试验品：参比品）的90%置信区间分别在80 - 125%和75 - 133%的接受范围内，则可判定为生物等效。
AUC(0,t)比值的90%置信区间（116.3% [109.6, 123.4%]）和C(max)比值的90%置信区间（114.4% [105.8, 123.8%]）均完全在接受范围内，且C(max)比值也符合80 - 125%的更窄界限。所研究的两种制剂的总体安全性概况无显著差异，对于未使用过阿片类药物的受试者而言，它们的耐受性良好，符合预期。
新型双层基质型贴片Fentalgon®在芬太尼暴露的速率和程度方面与单层基质型多瑞吉SMAT芬太尼贴片生物等效（欧盟临床试验编号：2005 - 000046 - 36）。
