萘普生胆碱离子液体在大鼠体内的药动学及生物利用度研究

Study on Pharmacokinetics and Bioavailability of Naproxen Choline Ionic Liquid in Rat

关键词:  萘普生  胆碱离子液体  药动学  生物利用度

Key words:  naproxen  choline ionic liquid  pharmacokinetics  bioavailability

摘要:

目的 研究萘普生胆碱离子液体灌胃给药后在大鼠体内的药动学和生物利用度。方法 采取灌胃给药的方式给予大鼠萘普生胆碱离子液体，于给药后不同时间点采集血样，血样经甲醇沉淀蛋白后离心，采用Extend-C₁₈色谱柱（4.6 mm×250 mm，5 μm），甲醇（A）-0.3%磷酸水溶液（B）（74：26）为流动相，流速为0.8 mL·min^–1，检测波长为230 nm，以吲哚美辛为内标液，萘普生为测定对象，分析大鼠体内血浆中萘普生胆碱离子液体的浓度。应用DAS 2.0软件拟合药动学参数。结果 大鼠灌胃给药萘普生混悬剂后t_1/2α为5.12 h，t_1/2β为10.13 h，T_max为2 h，C_max为112.92 mg·L^–1，AUC_（0-t）为1 091.01 mg·L^–1·h；大鼠灌胃给药萘普生胆碱离子液体后t_1/2α为5.64 h，t_1/2β为69.32 h，T_max为1 h，C_max为135.97 mg·L^–1，AUC_（0-t）为1 305.79 mg·L^–1·h，相对生物利用度为119.686%。结论 大鼠灌胃萘普生胆碱离子液体后，萘普生达峰时间提前，达峰浓度和生物利用度均高于萘普生混悬剂。

Abstract:

OBJECTIVE To investigate the pharmacokinetics and bioavailability of naproxen choline ionic liquid in rats after intragastric administration. METHODS Naproxen choline ionic liquid was given to rats by intragastric administration. Blood samples were collected at different time points after administration. The blood samples were precipitated by methanol and then centrifuged, and then an Extend-C₁₈ column(4.6 mm×250 mm, 5 μm) was used. Methanol(A)-0.3% phosphoric acid aqueous solution(B) (74:26) was used as the mobile phase, the flow rate was 0.8 mL·min^-1, and the detection wavelength was 230 nm. Indomethacin and naproxen were used as internal standard and tested object in determination of naproxen choline ionic liquid in rat plasma. Pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS After intragastric administration of naproxen suspension to rats, its t_1/2α was 5.12 h, t_1/2β was 10.13 h, T_maxwas 2 h, C_max was 112.92 mg·L^-1, and AUC_(0-t) was 1 091.01 mg·L^-1·h. After intragastric administration of naproxen choline, its t_1/2α was 5.64 h, t_1/2β was 69.32 h, T_max was 1 h, C_max was 135.97 mg·L^-1, AUC_(0-t) was 1 305.79 mg·L^-1·h, and the relative bioavailability was 119.686%. CONCLUSION After intragastric administration of naproxen choline to rats, the peak concentration and bioavailability of the naproxen in vivo are higher than those of the common suspension, and the peak time is earlier.