Carolinas Pain Institute and The Center for Clinical Research, 145 Kimel Park Dr, Ste 330, Winston-Salem, NC, 27103, USA.
Insys Development Company, Inc, Chandler, AZ, USA.
Clin Drug Investig. 2018 Aug;38(8):715-726. doi: 10.1007/s40261-018-0658-9.
Fentanyl sublingual spray may be a viable alternative to intravenous (IV) opioids for the treatment of acute pain. As patients with acute pain may include those who have limited prior exposure to opioids, this phase 1, open-label, randomized, multiple ascending-dose study was conducted to assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple doses of fentanyl sublingual spray in opioid-naïve participants. This article primarily reports the pharmacokinetics results.
Study drugs were administered in four dosing cohorts: every 0.5, 1, 2, or 4 h for a maximum of three doses per cohort. Eight fasted individuals per cohort were randomized to either fentanyl sublingual spray (100, 200, or 400 µg) or fentanyl citrate IV 50 µg (6:2 ratio). Blood samples were collected pre-dose through 24 h post first dose.
A total of 98 healthy adults were enrolled and 96 completed the study. Mean plasma fentanyl concentrations increased with increasing doses of fentanyl sublingual spray administered every 0.5-4 h. With multiple doses, systemic exposure increased relative to the first dose; shorter dosing intervals resulted in higher concentrations. Analysis of dose proportionality suggested that systemic exposure increased in a linear but slightly greater than dose-proportional manner. Accumulation between the first and last doses of fentanyl sublingual spray was more pronounced with shorter dosing intervals.
Dose-dependent fentanyl pharmacokinetics following multiple doses of fentanyl sublingual spray were well characterized in an opioid-naïve population. CLINICALTRIALS.
NCT02641340.
芬太尼舌下喷雾剂可能是治疗急性疼痛的静脉内（IV）阿片类药物的可行替代品。由于急性疼痛患者可能包括那些先前接触阿片类药物有限的患者，因此进行了这项 1 期、开放标签、随机、多次递增剂量研究，以评估多剂量芬太尼舌下喷雾剂在阿片类药物初治参与者中的药代动力学、药效学、安全性和耐受性。本文主要报告药代动力学结果。
在四个剂量组中给予研究药物：每 0.5、1、2 或 4 小时一次，每个剂量组最多给予三次。每个剂量组的 8 名禁食个体随机分为芬太尼舌下喷雾剂（100、200 或 400µg）或枸橼酸芬太尼 IV 50µg（6:2 比例）。在第一次给药前和首次给药后 24 小时内采集血样。
共有 98 名健康成年人入组，96 人完成了研究。芬太尼舌下喷雾剂每 0.5-4 小时给药一次，随着剂量的增加，平均血浆芬太尼浓度增加。随着多次给药，与首次剂量相比，全身暴露增加；较短的给药间隔导致更高的浓度。剂量比例分析表明，全身暴露以线性但略高于剂量比例的方式增加。芬太尼舌下喷雾剂的第一个和最后一个剂量之间的积累在较短的给药间隔下更为明显。
在阿片类药物初治人群中，多次给予芬太尼舌下喷雾剂后，芬太尼的药代动力学呈剂量依赖性。临床试验。
NCT02641340。
