喹烯酮及其主要代谢物在猪体内的药动学研究

摘要

Pharmacokinetics of quinocetone and its three main metabolites in swine were investigated in this study. Quinocetone was administered to 7 healthy cross-bread swine orally at a dosage of 40 mg/kg,The concentration of quinocetone and its major metabolites in plasma were detected using the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method,the concentration-time data were analyzed with WinNonlin5. 2 program. After oral administration, quinocetone and its three major metabolites were detected. Plasma drug concentration-time data of quinocetone after oral administration was found to be fitted to one compartment open model with first order absorption and its pharmacokinetic parameters were as follows: T1/2k = (0. 97±0.08)h,T1/2rz = (2. 79±0.16)h,CL=(26.03±0. 65)L/h· kg,Cmax=(0. 26±0.01),μg/ mL,Tmax=(2. 23±0. 06)h,AUC=(l. 54±0. 04)h o μg/mL. Plasma drug concentration-time data of demonoxyquinocetone and desoxyquinocetone were analyzed by non-compartmental model and its pharmacokinetic parameters were respectively as follows :demonoxyquinocetone, Tmax=(6. 33±1. 37)h,Cmax=(8. 81 ±2. 08) ng/mL,T1/2rz = (3. 03±1. 27)h,AUC=(0. 07± 0. 01)h- ng/mL,MRT=(6. 58±0. 40)h|desoxyquinocetone,Tmax=(10. 29±0. 29)h,Cmax= (6. 20±l. ll)ng/mL,T1/2rz= (5.84±2. 78)h, AUC= (0.15±0.01)h · ng/mL,MRT=(3. 64±0. 72)h. MQCA were detected in several samples. Quinocetone was rapidly absorbed and metabolized in swine after oral administration;three metabolites were detected,but their concentration were low.%本试验旨在研究喹烯酮及其主要代谢物在猪体内的药物代谢动力学过程.将喹烯酮按40 mg/kg的剂量对7头猪进行灌胃给药,采用HPLC-MS/MS法测定血浆中喹烯酮及其主要代谢物的浓度,药代动力学软件WinNonlin 5.2处理血浆中药物浓度一时间数据.灌胃给药后猪血浆中能检测到原药和N1-脱氧喹烯酮、脱二氧喹烯酮及3-甲基喹噁啉-2-羧酸(MQ-CA)3种代谢物,喹烯酮的浓度一时间数据符合一级吸收一室开放模型,其主要药代动力学参数为:T1/2Ks=(0.97±0.08)h,T1/2λz=(2.79±0.16)h,CL=(26.03±0.65)L/h·kg,Cmax=(0.26±0.01)μg/mL,Tmax=(2.23±0.06)h,AUC=(1.54±0.04)h·μg/mL；采用统计矩法处理N1-脱氧喹烯酮和脱二氧喹烯酮的浓度一时间数据,N1-脱氧喹烯酮主要药代动力学参数为:Tmax=(6.33±1.37)h,Cmax=(8.81±2.08) ng/mL,T1/2λs=(3.03±1.27)h,AUC=(0.07±0.01)h·ng/mL,MRT=(6.58±0.40)h；脱二氧喹烯酮的主要药动学参数:Tmax=(10.29±0.29)h,Cmax=(6.20±1.11)ng/mL,T1/2λs=(5.84±2.78)h,AUC=(0.15±0.01)h·ng/mL,MRT=(3.64±0.72)h.同时,在少数时间点检测到代谢物MQCA.猪口服喹烯酮后,吸收较快,消除较慢.血浆中检测到N1-脱氧喹烯酮、脱二氧喹烯酮及3-甲基喹噁啉-2-羧酸3种代谢物,且浓度较低、消除缓慢.