佐米曲普坦鼻喷雾剂与其片剂之间的相对生物利用度

Pharmacokinetics and relative bioavailability of domestic zolmitriptan nasal spray

目的研究国产佐米曲普坦鼻喷雾剂的人体药动学特性及与其口服制剂之间的相对生物利用度。方法采用双周期、开放、随机的自身交叉设计,20例健康志愿者分别单次口服参比制剂或鼻喷受试制剂各5 mg,用液相色谱串联质谱法测定血浆中佐米曲普坦的浓度,并采用DAS程序对试验数据进行处理,求算有关药动学参数和相对生物利用度。结果佐米曲普坦鼻喷雾剂和片剂的主要药动学参数:ρ_(max)分别为(10.44±3.59)、(12.16±2.85)μg·L^(-1),t_(max)分别为(3.18±1.32)、(2.21±1.26)h,t_(1/2)分别为(2.27±0.43)、(2.34±0.46)h,AUC_(0→15h)分别为(66.64±24.17)、(74.09±21.749)μg·h·L^(-1),AUC_(0→∞)分别为(68.02±24.59)、(76.02±22.68)μg·h·L^(-1);以AUC_(0→15h)计,单次鼻喷受试制剂的相对生物利用度为(89.47±17.03)%。单次给药后两者的ρ_(max)、AUC_(0→15h)、AUC_(0→∞)经对数转换后双单侧t检验,均在其等效标准范围内。t_(max)经Wilcoxon检验,差异有统计学意义,鼻喷雾剂比口服制剂达峰时间明显延后,但在给药后0.5 h内其吸收比口服制剂快。结论国产佐米曲普坦鼻喷剂相对于参比制剂具有生物等效性,同时具有吸收快,临床上可达到快速起效的优点。

AIM To study the Human pharmacokineties and relative bioavailability of zolmitriptan nasal spray. METHODS The bioequivalenee and relative bioavailability of a test preparation of zolmitriptan nasal spray in comparison with a imported reference preparation of tablet were investigated in a randomized openly two weeks cross-over study in 20 healthy volunteers following a single dose of 5 rng intranasal or oral medicine. Plasma coneentrations of zolmitriptan were determined by a LC-MS/MS system equipped with ultraviolet detection, and the test data were evaluated by DAS pro- gram. RESULTS The following pharmaeokinetie parameters were derived from the plasma eoneentration time courses, and the main parameters for test preparation and reference preparation were as follows： Pmax were（ 10.44 ± 3.59）and （12.16±2.85）μg L-1, tmaxWere（3.18±1.32）and（2.21± 1.26）h, tl/2were（2.27±O.43）and（2.34±O.46）h, AUC0-15sh were（66.64 ± 24.17）and（74.09 ± 21.749）μg h L- 1, AUC0 = were（68.02 ± 24.59） and（76.02 ± 22.68） /μg h L- l, respectively. Compared with reference preparation, the relative bioavailability for test preparation of a single intranasal dose was （89.47 ± 17.03）%, and the above parameters obtained from two kinds of drugs were compared. Double unilateral t test was carried out and no signifieant differences were found. The time to peak of nasal spray was significantly delayed than that of oral formulations after it deteeted by Wileoxon test, but the nasal spray had a faster ab- sorption than the other one after 0.5 h. CONCLUSION The home-made zolmitriptan nasal spray is bioequivalent with the imported reference preparation, and it can be effect instantly in the clinic owing to its fast absorption.