两种卡洛芬注射液在犬体内的生物等效性试验

doi:10.16431/j.cnki.1671-7236.2024.05.038

Abstract

Abstract: 【Objective】 The purpose of the experiment was to develop an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method,investigate the pharmacokinetic characteristics of two carprofen formulations in Beagle dogs,and evaluate the bioequivalence of two formulations.【Method】 Twenty-four beagle dogs were randomly allocated to two equal-sized treatment groups in a randomized dual-cycle and dual-sequence cross-over design.The test and the reference (RIMADYL^) formulations were subcutaneously administered in a single dose of 4.4 mg/kg BW.Blood samples were collected from brachiocephalic vein at 0,0.5,1,2,3,4,6,8,12,24,36,48 and 72 h after administration.The specificity,linearity,detection limit,quantification limit,accuracy,precision and stability of the UPLC-MS/MS method were investigated.The concentration of carprofen in plasma was determined by UPLC-MS/MS.The pharmacokinetic parameters (T_max,C_max,T_1/2 and AUC_0-t) and bioequivalence were calculated and analyzed by WinNonlin 8.1.【Result】 The methodological results showed good correlation over the concentration range of 10-5 000 ng/mL with a correlation coefficient(R²)≥0.99.The limit of detection and the limit of quantification were 5 and 10 ng/mL,respectively.Relative recoveries of high,medium,low and quantification limit concentrations were between 91.45%-111.61%.Coefficient variations of intra-assay and inter-assay were both less 15%.The pharmacokinetic parameters of two formulations were as follows:T_max were(2.27±1.09) and (2.33±1.10) h;C_max were (20.02±5.24) and (19.92±5.42) μg/mL;T_1/2 were (8.54±3.71) and (8.65±2.64) h;AUC_0-t were (246.78±55.94) and (249.22±53.33) μg·h/mL.The plasma profiles of carprofen following the administration of both formulations were similar.And the 90% CI of the average C_max,AUC_0-t and AUC_0-∞of the test/reference preparation were all fell between 80.00%-125.00%.【Conclusion】 The UPLC-MS/MS method established in this experiment was accurate and reliable,and could be used to determine the concentration of carprofen in plasma samples.The two formulations were bioequivalent for carprofen,and could be used clinically for the treatment of related diseases.The result of this study provided theoretical basis for clinical rational administration.

Key words: pharmacokinetic characteristics; bioequivalence; Beagle dog; carprofen injection; UPLC-MS/MS

CLC Number:

S859.7

ZHANG Lu, QIU Jicheng, GONG Xiaohui, CAO Yuying, KONG Jingyuan, CAO Xingyuan. Bioequivalence of Two Carprofen Formulations in Dogs[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(5): 2178-2187.

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Bioequivalence of Two Carprofen Formulations in Dogs

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