羟氯喹亚麻酸酯在Beagle犬的药代动力学

Pharmacokinetics of acid ester of hydroxychloroquine and linolenic acid in Beagle dogs

目的研究羟氯喹亚麻酸酯(AHQ)在Beagle犬体内的吸收行为特征以及在体内转化为羟氯喹的转化率。方法色谱柱:ASB C_(18)(50 mm×2. 1 mm,3μm),流动相为乙腈-0. 5%甲酸水溶液=55∶45,流速:0. 4 mL·min^(-1),进样量:50μL。6只Beagle,雌雄各半,单剂量静脉推注AHQ 3 mg·kg^(-1),采集血浆样本,用液相-串联质谱法测定血药浓度,用Win6. 2计算药代动力参数。结果 AHQ的主要药代动力学参数如下。t_(1/2)为(1. 5±0. 3) h,C_(max)为(1026. 0±149. 6)μg·mL^(-1),AUC_(0-t)为(639. 0±134. 6)μg·mL^(-1)·h,AUC_(0-inf)为(665. 0±142. 7)μg·mL^(-1)·h。结论 AHQ在Beagle犬体内具有快速消除的特点。

Objective To study the absorption behavior of acid ester of hydroxychloroquine and linolenic acid(AHQ)in Beagle dogs and the conversion rate of AHQ into hydroxychloroquine.Methods Chromatographic column C18(50 mm×2.1 mm,3μm)with the mobile phase is acetonitrile-0.5%formate aqueous solution=55∶45 at a flow rate of 0.4 mL·min-1.Single dose intravenous injection of 3 mg·kg-1 AHQ was performed in 6 Beagle dogs,each male and female.The injection volume was 50μL.After intravenous injection of Beagle dogs,plasma samples collected and it were measured by liquid phase-tandem mass spectrometry.The pharmacokinetic parameters were calculated by Win6.2 software.Results The pharmacokinetic parameters were as follows:t1/2 was(1.5±0.3)h,Cmaxwas(1026.0±149.6)μg·mL-1,AUC0-twas(639.0±134.6)μg·mL-1·h,AUC0-infwas(665.0±142.7)μg·mL-1·h.Conclusion AHQ shows fast elimination characteristics.