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目的:探讨平原组(P)与急进高原组(H)大鼠体内氨茶碱的药动学特征。方法:Wistar大鼠于平原地区禁食12 h后将0.003 8 g(约含氨茶碱3.6 mg)氨茶碱片剂灌胃给药,一周清洗期后急进高原,灌胃给药。平原组及急进高原组于给药前(0h)及给药后0.33,0.66,1,1.5,2,3,4,6,8,12,24 h由眼眶后静脉丛取血,采用液相-串联质谱方法测定血药浓度。结果:急进高原后,氨茶碱血浆超滤液浓度显著减低,因此蛋白结合率增高明显,平原组与高原组分别为37.05%和74.17%。氨茶碱急进高原组与平原组相比药动学参数发生显著变化,房室模型参数Ka显著增大,与高原组相比半衰期从(2.365±0.448)h增大到(2.944±0.694)h,体内平均驻留时间延长,峰浓度增大,达峰时间缩短,总清除率降低。结论:急进高原后,氨茶碱在大鼠体内代谢过程发生显著变化,研究结果为平原和急进高原后临床合理应用氨茶碱提供参考依据。
Objective: To investigate the pharmacokinetics of aminophylline in plain group (P) and acute plateau group (H) rats. METHODS: Wistar rats were orally administered with 0.003 8 g (about aminophylline 3.6 mg) of aminophylline tablets after a 12-hour fast in the plains. After a week of cleaning, the rats were rapidly taken to the plateau for gavage administration. In the plain group and the acute plateau group, blood was collected from the retro-orbital venous plexus before administration (0 h) and at 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after administration, Determination of plasma concentration by tandem mass spectrometry. Results: The concentration of aminophylline plasma ultrafiltrate was significantly decreased after acute plateau infection. Therefore, the protein binding rate increased significantly, which was 37.05% and 74.17% respectively in plain group and plateau group. Pharmacokinetic parameters of aminophylline in the plateau group were significantly different from those in the plains group, and the Ka parameter in atrioventricular model increased significantly from (2.365 ± 0.448) h to (2.944 ± 0.694) h , The average residence time in the body is prolonged, the peak concentration is increased, the peak time is shortened, and the total clearance rate is reduced. CONCLUSION: The aminophylline has a significant change in the metabolism process in rats after it is rapidly entering the plateau. The results provide a reference for the reasonable application of aminophylline in plain and acute plateau.