Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi`an, 710061, Shaanxi, China.
Xi'an Libang Pharmaceutical Co., Ltd., Xi'an, 710061, Shaanxi, China.
BMC Anesthesiol. 2022 Apr 21;22(1):113. doi: 10.1186/s12871-022-01653-1.
Ropivacaine oil delivery depot (RODD) can be used to treat postoperative incision pain. The aim was to study pharmacodynamics, toxicity and toxicokinetics of RODD.
The base research of RODD were conducted. Thirty rabbits were randomly divided into saline, solvent, ropivacaine aqueous injection (RAI) 0.9 mg, RODD 0.9 mg and RODD 3 mg groups. The sciatic nerve of rabbits were isolated, dripped with RODD and the effect of nerve block were observed. In toxicity study, the rats were divided into saline, solvent and RODD 75, 150 and 300 mg/kg groups, 30 rats per group. In toxicokinetics, rats were divided into RODD 75, 150 and 300 mg/kg groups, 18 rats per group. The rats were subcutaneously injected drugs.
The analgesic duration of RODD 3 mg and RAI 0.9 mg blocking ischiadic nerve lasted about 20 h and 2 h, respectively, and their blocking intensity was similar. The rats in RODD 75 mg/kg did not show any toxicity. Compared with saline group, in RODD 150 mg/kg group neutrophils and mononuclear cells increased, lymphocytes decreased and albumin decreased(P < 0.05), and pathological examination showed some abnormals. In RODD 300 mg/kg group, 10 rats died and showed some abnormalities in central nerve system, hematologic indexes, part of biochemical indexes, and the weights of spleen, liver, and thymus. However, these abnormal was largely recovered on 14 days after the dosing. The results of toxicokinetics of RODD 75 mg/kg group showed that the C was 1.24 ± 0.59 µg/mL and the AUC was 11.65 ± 1.58 h·µg/mL.
Subcutaneous injection RODD releases ropivacaine slowly, and shows a stable and longer analgesic effect with a large safety range.
罗哌卡因油剂贮库（RODD）可用于治疗术后切口疼痛。本研究旨在探讨 RODD 的药效学、毒性和毒代动力学。
进行了 RODD 的基础研究。将 30 只家兔随机分为生理盐水组、溶剂组、罗哌卡因水注射液（RAI）0.9mg 组、RODD 0.9mg 组和 RODD 3mg 组。分离家兔坐骨神经，滴注 RODD，观察神经阻滞效果。毒性研究中，将大鼠分为生理盐水组、溶剂组和 RODD 75、150 和 300mg/kg 组，每组 30 只。毒代动力学研究中，将大鼠分为 RODD 75、150 和 300mg/kg 组，每组 18 只。大鼠皮下注射药物。
RODD 3mg 和 RAI 0.9mg 阻滞坐骨神经的镇痛时间分别约为 20h 和 2h，阻滞强度相似。RODD 75mg/kg 组大鼠无毒性。与生理盐水组比较，RODD 150mg/kg 组大鼠中性粒细胞和单核细胞增多，淋巴细胞减少，白蛋白降低（P<0.05），病理检查显示部分异常。RODD 300mg/kg 组 10 只大鼠死亡，中枢神经系统、血液学指标、部分生化指标以及脾、肝、胸腺重量出现异常。但给药后 14 天，这些异常大部分恢复正常。RODD 75mg/kg 组毒代动力学结果显示，C 为 1.24±0.59µg/mL，AUC 为 11.65±1.58h·µg/mL。
RODD 皮下注射缓慢释放罗哌卡因，具有稳定且较长的镇痛作用，安全范围较大。
