PHARMACOKINETICS OF LOW-DOSE ORAL MODIFIED RELEASE, SOLUBLE AND INTRAVENOUS ASPIRIN IN MAN, AND EFFECTS ON PLATELET-FUNCTION
PHARMACOKINETICS OF LOW-DOSE ORAL MODIFIED RELEASE, SOLUBLE AND INTRAVENOUS ASPIRIN IN MAN, AND EFFECTS ON PLATELET-FUNCTION
复制标题
DOI：
10.1007/bf00558267
复制
发表时间：
1988-01-01
影响因子：
2.9
通讯作者：
LLOYD, JV
中科院分区：
文献类型：
--
作者：
BOCHNER, F;WILLIAMS, DB;LLOYD, JV
在6名健康志愿者中研究了低剂量阿司匹林和由此产生的水杨酸的药代动力学。每例受试者接受50 mg单次剂量的（1）口服缓释胶囊、（2）口服溶液和（3）静脉注射溶液。志愿者还每天接受50 mg改性释放胶囊，持续6天，以确定对胶原蛋白、ADP和花生四烯酸诱导的血小板聚集和血栓素产生的影响，并将重复给药后的药代动力学与单次给药后获得的参数进行比较。制剂和给药途径深刻地影响阿司匹林的几个药代动力学参数：最大浓度（Cmax，ng.单次给药和长期给药后的达峰时间（tmax，h）分别为221和191，口服溶液后为1323和6000，单次给药和长期给药后的达峰时间（tmax，h）分别为1.42和3.02，口服溶液后为0.29;血浆药物浓度对时间曲线下面积（AUC，μ g·cm·dot）。h.cntdot. ml-1）分别为0.38和0.27，口服溶液剂为0.68，静脉注射为1.57。两种溶液后阿司匹林的消除至少是双相的。终末相速率常数范围从静脉注射后的1.52 h-1至口服改性释放形式后的1.88 h-1。口服阿司匹林的吸收完全，尿中水杨酸的剂量完全恢复。水杨酸口服溶液和静脉注射的药代动力学参数显示相似的tmax和Cmax，但与阿司匹林一样，当使用修饰释放形式时，Cmax最小，tmax最大。在7天的修饰释放阿司匹林血小板聚集和血栓素的形成响应于胶原和花生四烯酸显着抑制。没有抑制ADP诱导的聚集，但血栓素的生产响应ADP被废除。
The pharmaocokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng .cntdot. ml-1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h was 1.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, .mu.g .cntdot. h .cntdot. ml-1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h-1 after intravenous injection to 1.88 h-1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as refelected by the total recoveryof the doses as salicylic acid in urine. The pharmacokinetic parameters for salicylic acid showed similar tmax and Cmax for the oral solution and intravenous injection but, as for aspirin, Cmax was lease and tmax greatest when the modified release form was used. After 7 days of modified release aspirin platelet aggregation and thromboxane formation in response to collagen and arachidonate were markedly inhibited. There was no inhibition of ADP-induced aggregation, but thromboxane production in response to ADP was abolished.