镁铝匹林在健康人体的药动学和药效学研究

 目的研究镁铝匹林在健康国人的药动学和药效学特征。方法选择健康汉族男性受试者28名,随机分成3个剂量组:81 mg·d^-1(n=9)、162mg·d^-1(n=9)及324mg·d^{-1(n=10),连续服药7d。采用HPLC-MS-MS测定血浆中阿司匹林及水杨酸浓度,采用ELISA法测定血浆血栓素B₂(TXB₂)浓度。结果阿司匹林t_max为30～40min,t_1/2为17.4～29.8min;水杨酸t_max为33.3～53.3min,t_1/2为168.2～209.6min。各组t_max,ρ_max,t_1/2,AUC和CL/F在给药d1和d7无显著性差异;t_1/2和CL/F在3组间无显著性差异。镁铝匹林抑制血小板TXB₂生成作用在3组间无显著性差异。结论在本试验剂量范围内,阿司匹林和水杨酸呈线性动力学,连续服药未见体内蓄积,抑制血小板活性作用相同。}

Pharmacokinetics and Pharmacodynamics of Aspirin After Single and Multiple Doses in Healthy Volunteers

OBJECTIVE To evaluate pharmacokinetics and pharmacodynamics of aluminium, magnesium and aspirin compound tablets in healthy volunteers. METHODS 28 Healthy volunteers were randomly assigned to three groups: 81 mg(n=9), 162 mg (n=9) and 324 mg(n=10). The test drug had 81 mg aspirin per tablet. All volunteers were orally administered everyday for successive 7 d. The plasma concentrations of aspirin and salicylic acid were determined by HPLC-MS-MS. Thromboxane B₂(TXB₂) was analyzed by ELISA.RESULTS The PK parameters of aspirin and salicylic acid were as follows:tmax 30～40 min and 33.3～53.3 min,t_1/2 17.4～29.8 min and 168.2～209.6 min,respectively. No significant differences in t_max,ρ_max,t_1/2,AUC and CL/F between day 1 and day 7,and t_1/2 and CL/F among three dosing groups were found .TXB₂ was inhibited by aspirin.The inhibiton of aspirin on TXB₂ was no significant difference among three dosing groups. CONCLUSION The linearity of aspirin and salicylic acid concentrations was shown in the three groups(81,162,324 mg) , and no drug accumulation was found after multiple doses were administered. Oral administrations of 81～324 mg aspirin showed the same inhibition on platelet.