Pharmacokinetics and Toxicity of Oily Delivery System of Ropivacaine via Subcutaneous Injection in Beagle Dogs

Background and Objective: Ropivacaine, a local anesthetic, can be used for postoperative analgesia but it has certain central and cardiovascular toxicity in high dose. This study investigated the pharmacokinetics and toxicity of oily delivery system ropivacaine in beagle dogs via subcutaneous injection. Materials and Methods: Twelve beagle dogs were randomly divided into ropivacaine oily delivery system and ropivacaine hydrochloride injection group (10 mg kgG 1 ). Liquid chromatography coupled with tandem mass spectrometry method was developed and validated for the determination of plasma ropivacaine. Fifty beagle dogs were divided into five groups, including saline injection group, ropivacaine oily delivery system (15, 30 and 60 mg kgG 1 ) groups and solvent group. The behaviors, pathological changes, electrocardiogram (ECG), blood cell counts, blood biochemistry, urine analysis and histopathological examination were observed. Results: The pharmacokinetic parameters of the oily delivery system of ropivacaine were calculated. The maximum plasma drug concentration (C max ) was 0.580.25 g mLG 1 ; the time to reach C max (T max ) was 11.01.6 h and the mean residence time (MRT) was 10.621.2 h. Compared with ropivacaine hydrochloride injection, the C max value was reduced by 80% and the T max and MRT values were substantially extended. There was no drug-related changes of toxicology, including behaviors, ECG, blood count, blood clotting, blood biochemistry and urine. Conclusion: Oily delivery system of ropivacaine was retained for longer time than ropivacaine hydrochloride solution in subcutaneous injection in beagle dogs and has no toxicity.