进食对健康受试者口服百可利咀嚼片药动学的影响

 目的 研究在进食和空腹状态下中国健康受试者口服百可利咀嚼片400 mg药动学的差异。方法 采用随机、双周期、自身交叉、安慰剂对照设计,12例健康受试者空腹或餐后口服百可利咀嚼片400 mg或安慰剂,HPLC-MS/MS测定血浆中百可利及其主要代谢物黄芩苷的浓度,计算其主要药动学参数并进行安全性评价。结果 受试者空腹和餐后口服单剂量百可利后,血浆中百可利的ρ_max分别为(15.752±9.328),(19.572±9.439) ng·mL^-1;AUC_0-t分别为(89.468±48.631),(122.073±28.285) ng·h·mL^-1;AUC_0-∞分别为(93.356±50.110),(126.212±28.270) ng·h·mL^-1。黄芩苷的ρ_max分别为(182.472±99.555),(154.782±100.834) ng·mL^-1;AUC_0-t分别为(1 193.230±693.408),(933.921±282.318) ng·h·mL^-1;AUC_(0-∞)分别为(1 266.425±866.664),(940.882±286.192) ng·h·mL^-1。空腹与餐后各发生4起不良事件,程度均为轻度。结论 与空腹服用400 mg百可利咀嚼片相比,进食后百可利的吸收程度增加,而黄芩苷的吸收降低。400 mg耐受性良好,空腹或进食下发生的不良事件相当。吸收程度的改变未影响药物的耐受性。

Effect of Food on the Pharmacokinetic Profile of Baicalein Chewable Tablets in Healthy Volunteers

OBJECTIVE To characterize the effects of food intake on the pharmacokinetic (PK) profile of oral baicalein chewable tablets at dose of 400 mg. METHODS In this randomized, 2-way crossover, placebo-control study, 12 healthy adult volunteers were assigned to receive a single dose of baicalein 400 mg or placebo after an overnight fast (fasted condition) or high-fat breakfast (fed condition). Concentrations of baicalein and its major metabolite baicalin in plasma were measured using HPLC-MS/MS. PK parameters were analyzed and safety was assessed. RESULTS The pharmacokinetic parameters of baicalein in fasted and fed states were as follows: ρ_max (15.752±9.328) vs (19.572±9.439) ng·mL^-1; AUC_0-t (89.468±48.631) vs (122.073±28.285) ng·h·mL^-1; AUC_0-∞ (93.356±50.110) vs (126.212±28.270) ng·h·mL^-1. The pharmacokinetic parameters of baicalin in fasted and fed states were as follows: ρ_max (182.472±99.555) vs (154.782±10.834) ng·mL^-1; AUC_0-t (1 193.230±693.408) vs (933.921±282.318) ng·h·mL^-1;AUC_(0-∞) (1 266.425±866.664) vs (940.882±286.192) ng·h·mL^-1. CONCLUSION The RESULTS of this study show that an increase in systemic exposure is observed for baicalein and a decrease in exposure is observed for baicalin when baicalein was taken with food. Baicalein 400 mg was generally well tolerated, with comparable adverse events in both the fed and the fasted states. The increase in exposure did not appear to impact the tolerability of the formulation.