Nexcyon Pharmaceuticals, Inc., Madison, Wisconsin, USA.
Deborah D. Linton, DL Veterinary Consulting, LLC, Rotonda West, Florida, USA.
J Vet Pharmacol Ther. 2022 Jul;45 Suppl 1:S40-S51. doi: 10.1111/jvp.13059.
A prospective, double-masked, placebo-controlled, multicentered phase 2 clinical study was conducted to select the transdermal buprenorphine solution (TBS) dosage for the control of postoperative pain in cats. One-hundred fifteen (115) cats were randomized to a single topical dose of placebo solution, low-TBS dosage (1.91-2.07 mg/kg) or high-TBS dosage (4.27-4.88 mg/kg) prior to surgical reproductive sterilization in conjunction with forelimb onychectomy. The low- and high-TBS doses were applied 2-4 and 1-2 hours prior to surgery. Interactive pain assessments and physiological variables were quantified through 96 hours post-anesthetic recovery and rescue analgesia was administered any time that analgesia was considered inadequate. Cats requiring rescue analgesia were considered treatment failures. The estimated overall treatment success rates from generalized linear mixed effects model analysis were 0.10 (95% CI: [0.02-0.36]), 0.56 (95% CI: [0.25-0.83]), 0.71 (95% CI: [0.38-0.91]) in the placebo-, low-, and high-TBS dose groups, respectively. Success rates for both TBS treatment groups were superior to placebo. Adverse events were infrequent in all treatment groups although the postoperative body temperatures over the duration of the study were on average 0.31 (95% CI: [0.08-0.55]) and 0.30 (95% CI: [0.05-0.53]) °C higher in low- and high-TBS dose cats, respectively, compared to placebo. It is concluded that both the low- and high-TBS dosages were safe and effective. The high-TBS dosage resulted in a greater proportion of treatment successes over 96 h, had a more acceptable preoperative application time of 1-2 h prior to surgery, and was therefore selected for further study.
一项前瞻性、双盲、安慰剂对照、多中心的 2 期临床研究旨在选择透皮丁丙诺啡溶液(TBS)的剂量,以控制猫的术后疼痛。115 只猫被随机分配接受单剂量安慰剂溶液、低 TBS 剂量(1.91-2.07mg/kg)或高 TBS 剂量(4.27-4.88mg/kg),然后进行外科生殖绝育手术和前肢趾切除术。低剂量和高剂量分别在手术前 2-4 小时和 1-2 小时给药。通过麻醉恢复后 96 小时的互动疼痛评估和生理变量进行量化,并在任何认为镇痛不足时给予补救镇痛。需要补救镇痛的猫被视为治疗失败。广义线性混合效应模型分析估计的总体治疗成功率分别为 0.10(95%CI:[0.02-0.36])、0.56(95%CI:[0.25-0.83])和 0.71(95%CI:[0.38-0.91])在安慰剂、低 TBS 和高 TBS 剂量组中。TBS 治疗组的成功率均优于安慰剂。所有治疗组的不良事件均不常见,尽管在研究过程中,低 TBS 和高 TBS 剂量猫的术后体温平均分别高 0.31(95%CI:[0.08-0.55])和 0.30(95%CI:[0.05-0.53])℃,但与安慰剂相比。结论是,低剂量和高剂量 TBS 均安全有效。高 TBS 剂量在 96 小时内有更高比例的治疗成功,术前应用时间可接受,为 1-2 小时,因此被选为进一步研究。