Fentanyl-induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5 months.
Fentanyl-induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5 months.
复制标题
芬太尼引起的啮齿动物呼吸抑制在 3.5 个月后可被生物可吸收的皮下纳曲酮植入物抑制。
DOI：
10.1111/adb.13350
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
Fishman,Marc
中科院分区：
文献类型：
--
作者：
Benner,JeffreyD;Cohen,StevenM;Hollenbaugh,JosephA;Fishman,Marc
本研究的目的是确定缓释、生物吸收的皮下埋植剂纳曲酮(NTX)是否能抑制静脉注射芬太尼后的呼吸抑制。将两种不同释放控制聚合物--聚-D-L-丙交酯和聚己内酯制成的可吸收植入物分别植入SD大鼠皮下。植入3.5月 后，通过尾静脉注射芬太尼。安慰剂植入大鼠接受4 微克(10 微克/公斤/剂量)，而NTX植入动物给予8 微克(20 微克/公斤/剂量)。对安慰剂植入的啮齿动物，芬太尼引起呼吸频率抑制的最小有效剂量为4 ； 50± 2%。植入安慰剂的大鼠的呼吸频率从给药前的2 0 8 ± 14次/分钟下降到2 分钟的84次± 12次/分钟(p= 0.0003)。相比之下，所有植入NTX的动物都很容易耐受两次8 微克剂量的芬太尼，而呼吸频率没有明显下降。平均呼吸频率 = 由给药前的16 4 ± 2 2次/分钟增加到2 时的1 78次± 17次/分钟(p= 0.2 4)。植入后3.5 ，平均血药浓度为7.4(±1.1)~80.3(±37.5)ng/mL。与安慰剂植入物相比，含有NTX的生物可吸收植入物在植入3.5月 后有效地阻断了芬太尼对啮齿动物的呼吸抑制。
The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release‐controlling polymers, poly‐D‐L‐lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5 months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4 micrograms (mcg) ‐ (10 mcg/kg/dose), while the NTX implanted animals received a dose of 8 mcg (20 mcg/kg/dose). Theminimum active dose of fentanylthat causeda> 50 ± 2% depression in the respiration rate in the placebo implanted rodents was 4 mcg. The respiration rate of the placebo implanted rats dropped from 208 ± 14 breaths/minute at predose, to 84 ± 12 breaths/minute (p= 0.0003) at 2 min. In contrast, all NTX implanted animals easily toleratedtwicethe dose of 8 mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate = increased from 164 ± 22 breaths/minute at predose to 178 ± 17 breaths/minute (p= 0.24) at 2 min. The mean plasma concentrations of NTX, 3.5 months after implantation, ranged from 7.4 (±1.1) ng/mL to 80.3 (±37.5) ng/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl‐induced respiratory depression in rodents as compared with placebo implants, 3.5 months after implantation.