高脂高热量饮食对中国健康受试者口服氟康唑片药动学的影响  

Effect of A High-Fat and High-calorie Diet on Pharmacokinetics of Fluconazole Tablets in Healthy Subjects in China

作　　者：郭彩会[1] 李颖[1] 孙雪 刘亚丽 宋浩静[1] 王祁民 董占军[1] GUO Caihui;LI Ying;SUN Xue;LIU Yali;SONG Haojing;WANG Qimin;DONG Zhanjun(Department of Pharmacy,Hebei General Hospital,Shijiazhuang 050051,China;Shijiazhuang Siyao Co.Ltd,Shijiazhuang 052100,China)

机构地区：[1]河北省人民医院药学部,石家庄050051 [2]石家庄四药有限公司,石家庄052100

出　　处：《医药导报》2022年第6期781-785,共5页Herald of Medicine

摘　　要：目的 观察中国健康受试者空腹和高脂高热量饮食情况下口服氟康唑片的药动学特征。方法 健康受试者分别在空腹或高脂高热量饮食条件下单剂量口服氟康唑片150 mg,其中空腹24例,餐后21例。分别在不同时间点采集静脉血样。用液相色谱-串联质谱(LC-MS/MS)法测定人血浆氟康唑浓度,用PhoenixWinNonlin7.0版软件按非房室模型计算药动学参数,用SPSS19.0版软件对空腹和餐后给药的主要药动学参数进行统计分析。结果 氟康唑片空腹和高脂高热量饮食后的主要药动学参数如下:峰浓度(C_(max))分别为(4052.92±723.38),(3373.33±439.46)ng·mL^(-1);半衰期(t_(1/2))分别为(29.52±4.16),(27.70±3.87)h;血药浓度-时间曲线下面积(AUC_(0-t))分别为(1.33±0.19)×10^(5),(1.28±0.20)×10^(5) ng·mL^(-1)·h;AUC_(0-∞)分别为(1.41±0.21)×10^(5),(1.35±0.22)×10^(5) ng·mL^(-1)·h;t_(max)中位数(范围)分别为1.00[0.25~3.00]h和3.00[1.00~6.00]h。高脂高热量饮食后服药较空腹条件下服药,AUC变化不明显,C_(max)降低16.77%(P<0.01),餐后服药的t_(max)明显延迟(P<0.01)。结论 食物对氟康唑的吸收速度有显著影响,对吸收程度无影响。Objective To evaluate the effects of fasting and high-fat and high calorie diet on the pharmacokinetics of fluconazole in Chinese healthy adult subjects.Methods Healthy subjects were assigned to receive a single dose of fluconazole tablets 150 mg in either fasting or high-fat and high-calorie diet condition,of which 24 were on fasting and 21 were postprandial.Blood samples were taken at different time points,and concentrations of fluconazole in plasma were determined by LC-MS/MS.Pharmacokinetic parameters were calculated by non-AV models with PhoenixWinNonlin7.0 software,and the main pharmacokinetic parameters of fasting and postprandial administration were statistically analyzed with SPSS19.0 software Results The main pharmacokinetic parameters of fluconazole in fasting state and high-fat diet and high-calorie state were as follows:C_(max) were(4052.92±723.38)and(3373.33±439.46)ng·mL^(-1);t_(1/2) were(29.52±4.16)and(27.70±3.87)h;AUC_(0-t) were(1.33±0.19)and(1.28±0.20)×10^(5) ng·mL^(-1)·h;AUC_(0-∞) were(1.41±0.21)and(1.35±0.22)×10^(5) ng·mL^(-1)·h;Median t_(max)(range)were 1.00[0.25,3.00]h and 3.00[1.00,6.00]h.Compared with the fasting condition,after a high-fat diet,the AUC was not significantly changed,and C_(max) was decreased by 16.77%(P<0.01),and t_(max) was significantly delayed(P<0.01).Conclusion Food had a significant effect on the absorption rate of fluconazole,but did not affect effect on the absorption degree.

关 键 词：氟康唑 高脂高热量饮食 药动学 食物效应 液相色谱-串联质谱 

分 类 号：R978.19[医药卫生—药品] R969.1[医药卫生—药学]