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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 lovastatin niacin sustained-release tablets in healthy volunteers. Methods: The experimental design of low-fat breakfast dose escalation, the cleaning period of 1 week. Twelve male and female healthy subjects were given oral low dose (niacin 500 mg / lovastatin 20 mg) and single oral dose of low dose nicotinic acid 500 mg / lovastatin 20 (Nicotinic acid 750 mg / lovastatin 20 mg), and a single dose of lovastatin niacin sustained-release tablets orally at a high dose (niacin 1000 mg / lovastatin 20 mg). Blood samples were taken before and after taking medicine at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4,5,6,8,10,12,14,24 h and plasma was separated. The concentrations of nicotinamide and its metabolites in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS / MS) and the concentration of lovastatin and the corresponding pharmacokinetic parameters were calculated. Results: After a single oral administration of lovastatin and niacin sustained-release tablets in healthy subjects, the doses of nicotinic acid ranged from 500 mg to 1 000 mg. The AUCs of 24 hours and Cmax of nicotinic acid, There is a linear relationship, and there is no gender difference. The cumulative constants of nicotinic acid, nicotinamide and tranexamic acid were (8.6 ± 8.6) (, 3.2, respectively) after taking continuous lovastatin niacin sustained release tablets (niacin 500 mg / lovastatin 20 mg) ± 1.2) and (5.6 ± 3.3). The main pharmacokinetic parameters of lovastatin did not change with the change of niacin dosage. The cumulative constant of multi-dose was (1.6 ± 0.6). CONCLUSION: Nicotinic acid and its metabolites nicotinamide and tranexamic acid show a linear pharmacokinetic profile in the human body after oral administration of nicotinic acid in the range of 500-1000 mg. After administration for several times, there is a significant accumulation in the body. There is no drug interaction between niacin and lovastatin.