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奥沙米特片健康人体药代动力学

Pharmacokinetics of oxatomide tablets in healthy Chinese volunteers

  • 摘要: 研究健康志愿者单次及多次口服奥沙米特片的药代动力学特征,并考察食物对其药代动力学的影响。单剂量试验采用拉丁方试验设计,12例受试者分别口服奥沙米特片30,60,120 mg,服药后0~48 h采集血样,清洗期1周。多剂量试验采用无参比1周给药设计,12例受试者每天7:00、19:00时各服奥沙米特片30 mg,连服至第7天晨,于第5~7天晨服药前及第7天晨服药后同上采集血样。进食影响试验两周期交叉试验设计,12例受试者分别空腹或饱腹口服奥沙米特片30 mg,服药后0~48 h采集血样,清洗期1周。采用HPLC-MS法测定血浆中奥沙米特浓度以及受试者给药后的血药浓度经时过程,该方法操作简单、专属性强、灵敏度高、准确性好。研究结果表明奥沙米特体内动力学行为符合线性药物动力学特征。多次给药与单次给药的药代动力学参数差异无统计学意义,表明多次给药后奥沙米特在体内基本无蓄积。进食会影响奥沙米特的吸收速率,但不影响其吸收程度。

     

    Abstract: The pharmacokinetics of oxatomide tablets in healthy Chinese volunteers after single and multiple-dose oral administration and the effect of food on it were studied.Single-dose study was carried out according to a replicated 3×3 Latin square design,with 12 volunteers orally receiving test tablets in single dose of 30 mg,60 mg and 120 mg,respectively.Blood samples were collected at specified time intervals up to 48 hours.The washout interval was 1 week.Multiple-dose study was carried out according to a 1-period design.Each volunteer orally received 30 mg oxatomide tablet twice daily (at 7:00 and 19:00) until the morning of the 7th day.Venous blood (4.0 mL) was drawn at the 5th and 6th mornings before administration to make sure that the steady state has appeared.On the 7th day,blood samples were collected again following the pre-specified time points after the last dose up to 48 h.After a washout period of 1 week,food effect was studied out according to an open,randomized,2-period crossover design.Oxatomide tablets (30 mg) were administered in fasting or eating state.The washout period was 1 week.Blood samples were collected at specified time intervals up to 48 hours.The plasma concentration-curves of oxatomide in this pharmacokinetic study were determined by a validated HPLC-MS method.The main pharmacokinetic parameters were calculated by software DAS 2.0.The validated method was proved to be simple,sensitive and rapid.The results exhibited that the absorption and disposition of oxatomide in human body followed the first order kinetics.There was no statistically significant difference between the phamacokinetic parameters of multiple- and single-dose study,which demonstrated that there was basically no accumulation of oxatomide in multiple-dose study.Food would affect the absorption rate of oxatomide,but not the extent of its absorption.

     

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