中国临床药学杂志

目的考察苯甲酸利扎曲普坦(RIZA)鼻腔给药制剂在大鼠体内的药动学过程,并与其静脉给药制剂和灌胃给药制剂相比较,评价制剂间主要药动学参数的变化。方法 15只SD大鼠分成3组,分别鼻腔给药、静脉注射和灌胃给予RIZA制剂,给药剂量为2.5 mg·kg^-1,采用高效液相-荧光检测方法测定大鼠血浆样品中RIZA的浓度,并计算主要药动学参数。结果大鼠鼻腔给药后的药动学参数:ρ_max为(608±67)μg·L^-1,t_max为(0.65±0.14)h,AUC_0-t为(1 380±87)μg·L^-1·h;大鼠静脉给药后的药动学参数:ρ_max为(1 135±110)μg·L^-1,AUC_0-t为(2 167±261)μg·L^-1·h;大鼠灌胃给药后的药动学参数:ρ_max为(144±28)μg·L^-1,t_max为(0.85±0.14)h,AUC_0-t为(442±110)μg·L^-1·h。鼻腔给药制剂相对于静脉给药制剂的绝对生物利用为63.68%,比灌胃给药制剂高2.12倍。结论鼻腔给药制剂相对于灌胃给药制剂有着较高的生物利用度,且比灌胃给药制剂起效迅速,预示该制剂有望提高偏头痛的治疗效果。本研究所建立的测定方法适用于RIZA大鼠体内药动学研究。

AIM To study the pharmacokinetic profiles of rizatriptan benzoate(RIZA) nasal solution in rats,and to compare the corresponding pharmacokinetic parameters with intravenous and oral formulations.METHODS Totally 15 SD rats were randomly divided into 3 groups,each group was intranasal,intravenous and oral administrated with RIZA at the dosage of 2.5 mg·kg^-1.The plasma concentration of RIZA was determined by HPLC method with fluorescence detection.Main pharmacokinetic parameters were calculated and statistically analyzed.RESULTS The main pharmacokinetic parameters of RIZA nasal solution were as follows:ρ_max were(608±67) μg·L^-1,t_max were(0.65±0.14) h,AUC_0-t were(1 380±87) μg·L^-1·h;the main pharmacokinetic parameters of RIZA intravenous injectionwere as follows:ρ_max were(1 135±110) μg·L^-1,AUC_0-t were(2 167±261) μg·L^-1·h;the main pharmacokinetic parameters of RIZA oral solution were as follows:ρ_max were(144±28) μg·L^-1,t_max were(0.85±0.14) h,AUC_0-t were(442±110) μg·L^-1·h.The absolute bioavailability of nasal solution was 63.68%,which was 2.12 times higher than the oral formulation.CONCLUSION The nasal formulation has a high bioavailability relative to the oral solution,indicating that the formulation is expected to improve the therapeutic effect of migraine.The HPLC method proved to be sensitive,specify and repeatable enough to be used in pharmacokinetic studies.