iX Biopharma Pty Ltd, Willetton, Western Australia.
Medical School.
Pain Med. 2019 Jan 1;20(1):143-152. doi: 10.1093/pm/pnx321.
The principal study objective was to investigate the pharmacokinetic characteristics and determine the absolute bioavailability and tolerability of a new sublingual (SL) buprenorphine wafer.
The study was of open label, two-way randomized crossover design in 14 fasted healthy male and female volunteers. Each participant, under naltrexone block, received either a single intravenous dose of 300 mcg of buprenorphine as a constant infusion over five minutes or a sublingual dose of 800 mcg of buprenorphine in two treatment periods separated by a seven-day washout period. Blood sampling for plasma drug assay was taken on 16 occasions throughout a 48-hour period (predose and at 10, 20, 30, and 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose). The pharmacokinetic parameters were determined by noncompartmental analyses of the buprenorphine plasma concentration-time profiles. Local tolerability was assessed using modified Likert scales.
The absolute bioavailability of SL buprenorphine was 45.4% (95% confidence interval = 37.8-54.3%). The median times to peak plasma concentration were 10 minutes and 60 minutes after IV and SL administration, respectively. The peak plasma concentration was 2.65 ng/mL and 0.74 ng/mL after IV and SL administration, respectively. The half-lives were 9.1 hours and 11.2 hours after IV and SL administration, respectively. The wafer had very good local tolerability.
This novel sublingual buprenorphine wafer has high bioavailability and reduced Tmax compared with other SL tablet formulations of buprenorphine. The wafer displayed very good local tolerability. The results suggest that this novel buprenorphine wafer may provide enhanced clinical utility in the management of both acute and chronic pain.
Buprenorphine is approved for use in pain management and opioid addiction. Sublingual administration of buprenorphine is a simple and noninvasive route of administration and has been available for many years. Improved sublingual formulations may lead to increased utilization of this useful drug for acute and chronic pain management.
主要研究目的是研究一种新的舌下（SL）丁丙诺啡片剂的药代动力学特征，并确定其绝对生物利用度和耐受性。
本研究为 14 名禁食健康男性和女性志愿者的开放标签、双交叉随机设计。在纳曲酮阻断下，每位参与者分别接受单次静脉注射 300 mcg 丁丙诺啡持续 5 分钟的恒速输注或舌下给予 800 mcg 丁丙诺啡，两种治疗期之间间隔 7 天洗脱期。在 48 小时内进行 16 次血样采集以进行血浆药物检测（给药前和给药后 10、20、30 和 45 分钟、1、1.5、2、2.5、3、4、6、8、12、24 和 48 小时）。通过非房室分析丁丙诺啡的血浆浓度-时间曲线来确定药代动力学参数。使用改良的李克特量表评估局部耐受性。
SL 丁丙诺啡的绝对生物利用度为 45.4%（95%置信区间=37.8-54.3%）。静脉注射和舌下给药后达到血浆峰浓度的中位数时间分别为 10 分钟和 60 分钟。静脉注射和舌下给药后的峰血浆浓度分别为 2.65ng/mL 和 0.74ng/mL。静脉注射和舌下给药后的半衰期分别为 9.1 小时和 11.2 小时。该片剂具有非常好的局部耐受性。
与其他丁丙诺啡舌下片剂制剂相比，这种新型舌下丁丙诺啡片剂具有更高的生物利用度和较短的 Tmax。该片剂具有非常好的局部耐受性。结果表明，这种新型丁丙诺啡片剂可能在急性和慢性疼痛管理中提供更好的临床效果。
丁丙诺啡已被批准用于疼痛管理和阿片类药物成瘾。丁丙诺啡舌下给药是一种简单且非侵入性的给药途径，已经使用了很多年。改进的舌下制剂可能会增加对这种有用药物的使用，以用于急性和慢性疼痛管理。
