Nycomed a Takeda Company, Konstanz, Germany.
Drug Deliv. 2013 Jun-Jul;20(5):216-23. doi: 10.3109/10717544.2012.762435. Epub 2013 May 8.
Intranasal fentanyl spray (INFS) was developed for the treatment of breakthrough pain in cancer patients using an alternative route of administration.
The aim of this clinical study was to investigate the pharmacokinetic (PK) profile and bioavailability of INFS in healthy subjects compared to oral transmucosal fentanyl citrate (OTFC).
In a randomized, single-center, open-label, two-way crossover PK study, 24 subjects (12 male, 12 female, mean age 25.2 years) received INFS (single-dose delivery system 200 μg/100 μl) and OTFC (buccal lozenge, 200 µg). Naltrexone was given to prevent potential adverse reactions. Frequent plasma samples were taken up to 96 h and analyzed by LC-MS/MS with a lower limit of quantitation of 25 pg/ml. Primary PK parameter was the area under the fentanyl plasma concentration-time curve (AUC(0-inf)).
Compared to OTFC, a much faster absorption rate was observed for INFS which was supported by the much earlier appearance of detectable fentanyl plasma levels and a shorter T(max). At 15 min post-dose, the mean plasma fentanyl levels reached 602 pg/ml for INFS and 29 pg/ml for OTFC. Significantly higher C(max) and AUC values were obtained with INFS compared to OTFC. Although administered for 15 min, consumption of OTFC was incomplete in many incidences (∼70%) upon visual inspection. No safety concerns were identified for fentanyl administration in combination with oral naltrexone.
One dose of INFS gives significantly higher plasma fentanyl levels and significantly higher bioavailability than OTFC based on dose-normalized AUC.
鼻腔芬太尼喷雾（INFS）是为治疗癌症患者的爆发性疼痛而开发的，采用了替代给药途径。
本临床研究旨在比较 INFS 与口腔黏膜芬太尼枸橼酸盐（OTFC）在健康受试者中的药代动力学（PK）特征和生物利用度。
在一项随机、单中心、开放标签、两交叉 PK 研究中，24 名受试者（12 名男性，12 名女性，平均年龄 25.2 岁）接受了 INFS（单次剂量输送系统 200μg/100μl）和 OTFC（颊含片，200μg）。给予纳曲酮以预防潜在的不良反应。频繁采集血浆样本，时间长达 96 小时，并通过 LC-MS/MS 进行分析，定量下限为 25pg/ml。主要 PK 参数为芬太尼血浆浓度-时间曲线下面积（AUC(0-inf)）。
与 OTFC 相比，INFS 的吸收速度更快，这得到了更早出现可检测到的芬太尼血浆水平和更短的 T(max)的支持。在给药后 15 分钟，INFS 的平均血浆芬太尼水平达到 602pg/ml，而 OTFC 为 29pg/ml。与 OTFC 相比，INFS 获得了更高的 C(max)和 AUC 值。尽管仅给药 15 分钟，但在许多情况下（约 70%）通过目视检查发现 OTFC 的消耗不完全。芬太尼与口服纳曲酮联合使用未发现安全性问题。
INFS 单次给药的血浆芬太尼水平明显高于 OTFC，基于剂量归一化 AUC，生物利用度也明显更高。
