Nexcyon Pharmaceuticals, Inc., Madison, Wisconsin, USA.
East Tennessee Clinical Research, Inc., Rockwood, Tennessee, USA.
J Vet Pharmacol Ther. 2022 Jul;45 Suppl 1:S31-S39. doi: 10.1111/jvp.13044.
A novel transdermal buprenorphine solution (TBS) was developed for evaluation in order to make available an extended duration opioid analgesic for cats. Healthy adult cats were administered a single TBS dose of 10 mg (1.57-4.35 mg/kg), 30 mg (4.72-13.0 mg/kg), or 50 mg (7.87-21.7 mg/kg) (4 cats per group) applied topically to the unclipped dorsal cervical skin and plasma buprenorphine concentrations were evaluated through 7 days. To determine the absolute bioavailability of TBS, healthy cats were administered single TBS dose of 20 mg (3.33-4.76 mg/kg) or 0.05 mg (0.008-0.011 mg/kg) IV buprenorphine (6 cats per group). The mean ± standard deviation maximum plasma buprenorphine concentrations (C ) were 10.5 ± 6.28, 18.6 ± 8.68, and 22.5 ± 4.47 ng/ml following 10, 30, and 50 mg doses, respectively, with the time of C occurrence (t ) typically occurring at 2-12 h post-dosing. Mean plasma buprenorphine terminal half-lives ranged between 78.3 and 91.2 h. Increasing the dose threefold and fivefold from the 10 mg dose increased the exposure by 2.8- and 3.6-fold, respectively, indicating that plasma buprenorphine exposure increased in a less than proportional manner at doses >30 mg. Transient sedation, mydriasis, and euphoria were observed within 4 h post-dosing. Mean rectal temperatures were increased 0.6-0.9°C greater than baseline (37.4-37.8°C) through 168 h post-dosing. The absolute bioavailability was 16.0% (90% CI: [11.8%-21.7%]). Flip-flop pharmacokinetics were observed with a terminal elimination half-life of 0.82 ± 0.13 and 64.9 ± 15.0 h for IV buprenorphine and 20 mg of TBS, respectively. A single administration of TBS over a range of doses resulted in extended plasma buprenorphine concentrations and opioid physiological and behavioral effects.
一种新型经皮丁丙诺啡溶液（TBS）被开发用于评估，目的是为猫提供一种延长作用时间的阿片类镇痛药。健康成年猫接受单次 TBS 剂量为 10mg（1.57-4.35mg/kg）、30mg（4.72-13.0mg/kg）或 50mg（7.87-21.7mg/kg）（每组 4 只猫），经皮涂于未修剪的颈背皮肤，通过 7 天评估血浆丁丙诺啡浓度。为了确定 TBS 的绝对生物利用度，健康猫接受单次 TBS 剂量为 20mg（3.33-4.76mg/kg）或 IV 丁丙诺啡 0.05mg（0.008-0.011mg/kg）（每组 6 只猫）。C 的最大平均±标准偏差血浆丁丙诺啡浓度（）分别为 10.5±6.28、18.6±8.68 和 22.5±4.47ng/ml，剂量分别为 10、30 和 50mg，C 发生的时间（）通常在给药后 2-12 小时。平均血浆丁丙诺啡终末半衰期在 78.3 和 91.2 小时之间。与 10mg 剂量相比，剂量增加两倍和三倍分别使暴露量增加 2.8 倍和 3.6 倍，表明在>30mg 剂量时，血浆丁丙诺啡暴露量呈不成比例增加。在给药后 4 小时内观察到短暂镇静、散瞳和欣快感。与基线（37.4-37.8°C）相比，直肠温度升高 0.6-0.9°C，持续 168 小时。绝对生物利用度为 16.0%（90%CI：[11.8%-21.7%]）。翻转药代动力学观察到丁丙诺啡的终末消除半衰期为 0.82±0.13 小时和 TBS 20mg 的 64.9±15.0 小时。单次 TBS 给药在一定剂量范围内可延长血浆丁丙诺啡浓度和阿片类药物的生理和行为效应。
