洛伐他汀烟酸缓释片健康人体药动学研究  

Pharmacokinetics of niacin extended-release/lovastatin tablets in healthy volunteers

作　　者：王玉[1] 宋敏[1] 杭太俊[1] 阙小亭[1] 王珵[1] 文爱东[2] 杨林[2] 

机构地区：[1]中国药科大学药学院药物分析教研室,南京210009 [2]中国人民解放军第四军医大学西京医院国家药品临床试验机构,西安710032

出　　处：《中国新药杂志》2011年第5期433-439,共7页Chinese Journal of New Drugs

摘　　要：目的:研究洛伐他汀烟酸缓释片在健康人体内的药动学。方法:采用低脂早餐后剂量递增实验设计,清洗期为1周。健康受试者12名,男女各半,分别单剂量口服低剂量(烟酸500 mg/洛伐他汀20mg);连续7 d,qd,多次口服低剂量(烟酸500 mg/洛伐他汀20 mg);单剂量口服中剂量(烟酸750 mg/洛伐他汀20 mg);单剂量口服高剂量(烟酸1 000 mg/洛伐他汀20 mg)的洛伐他汀烟酸缓释片。采集服药前及服药后0.5,1,1.5,2,2.5,3,3.5,4,5,6,8,10,12,14,24 h血样,分离血浆。采用液相色谱-串联质谱法(LC-MS/MS)分别测定血浆中烟酸及其代谢物烟酰胺和烟脲酸浓度以及洛伐他汀浓度,并计算相应药动学参数。结果:健康受试者单次口服洛伐他汀烟酸缓释片后,烟酸剂量在500～1 000 mg范围内,烟酸、烟酰胺和烟脲酸的AUC0～24 h和Cmax均与剂量呈线性关系,且不存在性别差异。连续多次服用洛伐他汀烟酸缓释片(烟酸500 mg/洛伐他汀20 mg)7 d后,烟酸、烟酰胺和烟脲酸的蓄积常数分别为(8.6±8.6)(,3.2±1.2)和(5.6±3.3)。洛伐他汀的主要药动学参数不随烟酸剂量变化而改变,多剂量的蓄积常数为(1.6±0.6)。结论:口服烟酸剂量在500～1 000 mg范围内,烟酸及其代谢物烟酰胺和烟脲酸在中国人体内均呈线性药动学特征,多次给药后在体内有明显蓄积。烟酸和洛伐他汀之间不存在药物相互作用。Objective：To study the pharmacokinetics of niacin extended-release/lovastatin tablets with single and multiple oral doses in healthy Chinese volunteers.Methods：The study was carried out with an incremental dosage design after an overnight fast and light fat breakfast,and wash-out period was one week.In 12 Chinese healthy volunteers,single oral doses of niacin extended-release/lovastatin tablets（500 mg/20 mg）,multiple oral doses of 500 mg/20 mg qd for 7 consecutive days,single oral doses of 750 mg/20 mg and 1 000 mg/20 mg were administered,respectively.The blood samples were taken just before and 0.5,1,1.5,2,2.5,3,3.5,4,5,6,8,10,12,14,24 h after the administration.The plasma concentrations of niacin（NA）,niacinamide（NAM）,nicotinuric acid（NUR） and lovastatin were determined by validated LC-MS/MS methods,and the pharmacokinetic parameters were evaluated.Results：In the range of 500~1 000 mg of the niacin extended-release/lovastatin tablets,the AUC0~24 h and Cmax of NA,NAM and NUR had good linearity with the doses after single oral administrations.No significant gender differences were found for them.The observed accumulation index values of NA,NAM and NUR after multiple oral administrations of 500 mg/20 mg niacin extended-release/lovastatin tablets were（8.6±8.6）,（3.2±1.2） and（5.6±3.3）,respectively.The pharmacokinetics of lovastatin was not affected by the dosages of NA,and the accumulation index value was（1.6±0.6） after multiple doses.Conclusion：NA and its metabolites demonstrate linear pharmacokinetics in the dose range studied.The drug accumulation after multiple oral doses is significant.No drug interaction has been found between niacin and lovastatin.

关 键 词：洛伐他汀烟酸缓释片 烟酸 烟酰胺 烟脲酸 洛伐他汀 药动学 液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学] R972.6[医药卫生—药学]