Perelman Michael, Fisher Anthony N, Smith Alan, Knight Alastair
ARchimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, Nottingham, UK.
Int J Clin Pharmacol Ther. 2013 May;51(5):349-56. doi: 10.5414/CP201825.
Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety.
Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period.
A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml).
Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.
芬太尼果胶鼻喷雾剂（FPNS，在美国为Lazanda®，在欧洲和澳大利亚为PecFent®）是一种新型镇痛药，已被批准用于治疗癌症患者的突破性疼痛。鉴于芬太尼通过鼻腔给药，了解合并过敏性鼻炎或使用血管收缩剂对其进行治疗是否会影响其吸收，以及可能影响其疗效或安全性，这一点很重要。
对有过敏性鼻炎病史的受试者进行筛查，以确定在环境暴露舱（EEC）中接触花粉过敏原（豚草或树木）时至少出现中度鼻炎症状的受试者。这些受试者进入一项随机、三交叉研究，其中每个受试者在三种暴露条件下接受100μg的FPNS；对照（无鼻炎）、鼻炎（有症状但未使用减充血剂）、治疗（有症状且同时使用羟甲唑啉）。在24小时内采集芬太尼血样。
共筛查了132名受试者，确定54名受试者纳入研究；31名受试者可进行药代动力学评估。对照和鼻炎条件下芬太尼吸收的测量值（均值或中位数）相似：Cmax分别为453.0与467.8pg/ml；AUCt分别为1292.3与1325.4pg×h/ml，AUC0-∞分别为1430.6与1387pg×h/ml，tmax分别为20与17分钟。当同时使用羟甲唑啉时，芬太尼的总体吸收略有降低（AUC0-∞为1362.4pg×h/ml）；但更具临床相关性的是吸收速率延迟（tmax为53分钟）和Cmax降低（235.3pg/ml）。
接受FPNS治疗的患者不会受到过敏性鼻炎发展的影响；但是，如果开了羟甲唑啉，患者在开始和停止使用羟甲唑啉时增加监护会受益。
