洛伐他汀烟酸缓释片人体药物代谢动力学研究  

Pharmacokinetic Study of Lovastatin/niacin Sustained-release Tablets in Healthy Chinese Volunteers

作　　者：罗柱[1] 梁茂植[1] 王颖[1] 余勤[1] 沈奇[1] 秦永平[1] 

机构地区：[1]四川大学华西医院国家药物临床试验机构/GCP中心,成都610041

出　　处：《华西医学》2015年第10期1881-1886,共6页West China Medical Journal

摘　　要：目的研究洛伐他汀烟酸缓释片在中国健康受试者体内的药物代谢动力学特征。方法单次给药每周期分别口服洛伐他汀烟酸缓释片20/500、20/750、20/1 000 mg;连续给药每次口服洛伐他汀烟酸缓释片20/1 000 mg,1次/d,连续5 d。每周期给药前及给药后10、20、30、45 min,1、1.5、2、2.5、3、3.5、4、5、7、9、12、15 h采集血样。采用高效液相色谱-串联质谱法检测血浆中洛伐他汀、烟酸及其代谢产物烟酰胺和烟脲酸的浓度。结果烟酸在500～1 000 mg剂量范围内,烟脲酸峰浓度和药-时曲线下面积（0-t）与剂量呈线性关系;连续给药情况下,烟脲酸和洛伐他汀在体内没有蓄积;不同配比的烟酸组分对洛伐他汀的体内代谢无影响;男女受试者药物代谢动力学参数差异无统计学意义（P〉0.05）。结论洛伐他汀烟酸缓释片具备线性动力学特征,连续给药无蓄积,代谢不受性别影响。Objective To study the pharmacokinetics of lovastatin/niacin sustained-release tablets in healthy Chinese volunteers. Methods Eligible subjects were enrolled to receive a single dose of 20/500, 20/750 and 20/1 000 mg lovastatin/niacin sustained-release tablets and multiple dose of 20/1 000 mg lovastatin/niacin sustainedrelease tablets, one time per day, sustained for 5 days, respectively. Blood samples were obtained before dosing and up to 10, 20, 30, and 45 minutes, and 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, and 15 hours after dosing. Niacin, niacinamide, nicotinuric acid and lovastatin were detected by high performance liquid chromatography-tandem mass spectrometry method. Results The peak concertration and the area under the plasma concentration-time curve（0-t） of nicotinuric acid had linear dynamics characteristics with the dosage when the dose of niacin was between 500 and 1 000 mg. After multiple dosing, pharmacokinetics parameters of nicotinuric acid and lovastatin were close. No significant difference was found between male and female subjects. Conclusions Lovastatin/niacin sustained-release tablets possess linear kinetics. Accumulation is not significant after multiple dosing. Gender doesn＇t affect the pharmacokinetics parameters.

关 键 词：洛伐他汀烟酸缓释片 高效液相色谱-串联质谱法 药物代谢动力学 

分 类 号：R969.1[医药卫生—药理学]