Pharmacodynamics, toxicology and toxicokinetics of ropivacaine oil delivery depot

Abstract Background: Ropivacaine oil delivery depot (RODD) can be used to treat postoperative incision pain. The aim was to study pharmacodynamics, toxicity and toxicokinetics of RODD. Methods: 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. Results: 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 were similar. The rats in RODD 75 mg/kg did not show any toxicity. RODD 150 mg/kg group compared with saline 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 Cmax was 1.24±0.59 µg/mL and the AUC(0-24h) was 11.65±1.58 h·µg/mL. Conclusions: Subcutaneous injection RODD in rats released ropivacaine slowly, and showed a stable and longer analgesic effect with a large safety range.