PRA Health Sciences, Salt Lake City, UT, USA.
BioDelivery Sciences International, Inc., Raleigh, NC, USA.
Adv Ther. 2020 Nov;37(11):4685-4696. doi: 10.1007/s12325-020-01481-0. Epub 2020 Sep 25.
Buprenorphine is a partial μ-opioid receptor agonist that, unlike full μ-opioid receptor agonists, has been shown to have a ceiling effect on respiratory depression. Buprenorphine buccal film (BBF) is approved by the US Food and Drug Administration for use in patients with chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment and for whom alternative treatment options are inadequate. This study was conducted to compare the effects of BBF and immediate-release oral oxycodone hydrochloride administration on respiratory drive, as measured by the ventilatory response to hypercapnia (VRH) after drug administration.
Subjects (N = 19) were men and women, ages 27-41 years, self-identifying as recreational opioid users who were not physically dependent on opioids as determined via a Naloxone Challenge Test. Respiratory drive was evaluated by measuring VRH through the assessment of the maximum decrease in minute ventilation (E) after administration of each treatment. The treatments utilized in this study included 300, 600, and 900 μg BBF; 30 and 60 mg orally administered oxycodone; and placebo (each separated by a 7-day washout period). Effects on respiratory drive were assessed using a double-blind, double-dummy, six-treatment, six-period, placebo-controlled, randomized crossover design. Statistical analyses were performed using a linear mixed-effects model.
The least squares mean differences in minute volume E (L/min, versus placebo) were as follows: 300 μg BBF (+ 1.24, P = 0.529), 600 μg BBF (+ 0.23, P = 0.908), 900 μg BBF (+ 0.93, P = 0.637), 30 mg oxycodone (- 0.79, P = 0.687), and 60 mg oxycodone (- 5.23, P = 0.010).
BBF did not significantly reduce respiratory drive at any dose compared with placebo, including at the maximum available prescription dose of 900 μg. Administration of oxycodone resulted in a significant dose-dependent decrease in respiratory drive. These data suggest that BBF may be a safer treatment option than full μ-opioid receptor agonists for patients with chronic pain.
ClinicalTrials.gov identifier, NCT03996694.
丁丙诺啡是一种部分 μ-阿片受体激动剂，与完全 μ-阿片受体激动剂不同，它对呼吸抑制有上限效应。丁丙诺啡颊膜片（BBF）已获得美国食品和药物管理局批准，用于治疗疼痛剧烈、需要每日 24 小时、长期使用阿片类药物治疗且其他治疗选择不足的慢性疼痛患者。本研究旨在比较 BBF 和即释口服盐酸羟考酮给药后对呼吸驱动的影响，通过给药后对高碳酸血症的通气反应（VRH）来测量呼吸驱动。
受试者（N=19）为年龄在 27-41 岁之间的男性和女性，自我认定为娱乐性阿片类药物使用者，通过纳洛酮挑战测试确定他们没有身体上对阿片类药物的依赖。呼吸驱动通过测量给药后分钟通气量（E）的最大下降来评估 VRH。本研究中使用的治疗方法包括 300、600 和 900μg BBF；30 和 60mg 口服羟考酮；和安慰剂（每个治疗组之间间隔 7 天洗脱期）。使用双盲、双模拟、六治疗、六周期、安慰剂对照、随机交叉设计评估对呼吸驱动的影响。统计分析采用线性混合效应模型。
与安慰剂相比，分钟容积 E（L/min，与安慰剂相比）的最小二乘均值差异如下：300μg BBF（+1.24，P=0.529），600μg BBF（+0.23，P=0.908），900μg BBF（+0.93，P=0.637），30mg 羟考酮（-0.79，P=0.687），60mg 羟考酮（-5.23，P=0.010）。
与安慰剂相比，BBF 在任何剂量下均未显著降低呼吸驱动，包括最大可用处方剂量 900μg。羟考酮的给药导致呼吸驱动呈剂量依赖性下降。这些数据表明，与完全 μ-阿片受体激动剂相比，BBF 可能是慢性疼痛患者更安全的治疗选择。
ClinicalTrials.gov 标识符，NCT03996694。
