用化学发光微粒子免疫法研究甲钴胺在人体内的药动学和生物等效性

 目的建立甲钴胺人体内血药浓度的化学发光微粒子免疫测定方法,并对口服甲钴胺制剂后人体内的药动学和生物等效性进行研究。方法采用本试验建立的化学发光微粒子免疫法测定血清中甲钴胺的浓度,并对20名健康受试者口服单剂量1 500μg甲钴胺胶囊后的试验数据进行处理。结果口服试验制剂甲钴胺胶囊和参比制剂后的ρ_max分别为(511.30±172.71)和(580.15±194.46)ng·L^-1;血清中甲钴胺浓度增加量的△ρ_max分别为(192.10±58.44)和(235.35±90.33)ng·L^-1;t_max分别为(4.33±2.61)和(4.55±2.94)h;t_1/2分别为(18.09±5.56)和(19.26±7.56)h;△AUC_0-t分别为(5 566.35±2620.19)和(5 411.78±2 676.79)ng·h·L^-1,△AUC_0-∞分别为(6 724.17±2 098.16)和(6 324.02±1 978.00)ng·h·L^-1;口服甲钴胺试验制剂后相对生物利用度F_0-t和F_0-∞分别为(106.49±28.90)%和(107.81±26.10)%。经拟合,口服甲钴胺制剂后其血药浓度-时间数据符合权重因子为1/C²的口服二室模型。结论本试验建立的甲钴胺人体内血药浓度的测定方法简便、可靠,测定灵敏度高,试验制剂甲钴胺胶囊和参比制剂生物等效。

Chemiluminescent Microparticle Immunoassay for Investigation of Pharmacokinetics and Bioequivalence of Mecobalamin

OBJECTIVE To establish a chemiluminescent microparticle immunoassay(CMIA) method for determination of mecobalamin in serum,and investigate the pharmacokinetics and bioequivalence of mecobalamin.METHODS The chemiluminescent microparticle immunoassay method was used to assay the concentration of mecobalamin in serum,the pharmacokinetics and bioequivalence of mecobalamin were evaluated.RESULTS The main pharmacokinetic parameters of the mecobalamin capsules and reference tablets by oral administration were as follows:ρ_max(511.30±172.71) vs(580.15±194.46) ng·L^-1;△ρ_max(192.10±58.44) vs.(235.35±90.33) ng·L^-1;t_max(4.33±2.61) vs.(4.55±2.94)h;t_1/2(18.09±5.56) vs(19.26±7.56)h;△AUC_0-t(5 566.35±2 620.19) vs.(5 411.78±2 676.79) ng·h·L^-1;△AUC_0-∞ (6 724.17±2 098.16) vs(6 324.02±1 978.00) ng·h·L^-1;F_0-t(106.49±28.90)%;F_0–∞(107.81±26.10)%.The pharmacokinetic parameters were estimated by a two-compartment model with first-order absorption and elimination.CONCLUSION The study established a simple,reliable and highly sensitive method for the determination of mecobalamin level in serum.The test capsules are bioequivalent to the reference tablets.