盐酸文拉法辛缓释片Beagle犬体内药动学及生物等效性研究
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摘要
目的研究盐酸文拉法辛缓释片在Beagle犬体内的药动学和生物等效性。方法 8条健康Beagle犬随机分成2组,采用双周期、双交叉、单剂量分别ig盐酸文拉法辛缓释片受试制剂或参比制剂75 mg,清洗期为1周;建立血浆中盐酸文拉法辛液相色谱-质谱联用(LC-MS/MS)检测方法,进行方法精密度、准确度、提取回收率、基质效应、稳定性方法学验证;测定给药前(0 h)及给药后2、3、4、5、6、8、10、12、14、16、24、36、48、72 h血浆中盐酸文拉法辛血药浓度,运用DAS 2.1.1软件计算其药动学参数,并评价其生物等效性。结果 LC-MS/MS方法学经验证符合检测要求,受试制剂和参比制剂主要药动学参数分别如下:T1/2分别为(7.16±2.34)和(6.95±1.57)h、Cmax分别为(522.89±201.12)和(515.22±159.29)ng/mL、Tmax分别为(10.38±1.69)和(10.50±2.07)h、AUC0-t分别为(8 398.64±3332.86)和(8 050.71±2103.15)ng?h/mL、AUC0-∞分别为(8 701.60±3303.29)和(8 450.01±2273.45)ng?h/mL;以参比制剂为参考,受试制剂AUC0-∞相对生物利用度为(101.0±13.1)%。结论盐酸文拉法辛缓释片受试制剂与参比制剂在Beagle犬体内具有生物等效性。
Objective To investigate the pharmacokinetic profiles and bioequivalence of Venlafaxine hydrochloride sustained release tablets.Methods Eight healthy Beagle dogs were ig given Venlafaxine hydrochloride sustained-release tablets or reference tablets of75 mg in two-cycle,double-crossover and single-dose respectively.A method for the determination of Venlafaxine hydrochloride in plasma by LC-MS/MS was established.The method was validated for precision,accuracy,recovery,matrix effect and stability.The blood concentration of Venlafaxine hydrochloride in plasma was determined before(0 h) and 2,3,4,5,6,8,10,12,14,16,24,36,48,72 h after administration.The pharmacokinetic parameters were calculated by DAS 2.1.1 and its bioequivalence was evaluated.Results LC-MS/MS methodologies were verified to meet the detection requirements.The main pharmacokinetic parameters of Venlafaxine test and reference preparations were as follows:T1/2,(7.16±2.34) and(6.95±1.57) h;Cmax,(522.89±201.12) and(515.22±159.29) ng/mL;Tmax,(10.38±1.69) and(10.50±2.07) h;AUC0-t,(8 398.64±3 332.86) and(8 050.71±2 103.15) ng·h/mL;AUC0-∞,(8701.60±3 303.29) and(8 450.01±2 273.45) ng·h/mL,respectively.The relative bioavailability of Venlafaxinewas(101.0±13.1)%.Conclusion Venlafaxine hydrochloride sustained-release tablets have bioequivalence with reference tablets in Beagle dogs.
Objective To investigate the pharmacokinetic profiles and bioequivalence of Venlafaxine hydrochloride sustained release tablets.Methods Eight healthy Beagle dogs were ig given Venlafaxine hydrochloride sustained-release tablets or reference tablets of75 mg in two-cycle,double-crossover and single-dose respectively.A method for the determination of Venlafaxine hydrochloride in plasma by LC-MS/MS was established.The method was validated for precision,accuracy,recovery,matrix effect and stability.The blood concentration of Venlafaxine hydrochloride in plasma was determined before(0 h) and 2,3,4,5,6,8,10,12,14,16,24,36,48,72 h after administration.The pharmacokinetic parameters were calculated by DAS 2.1.1 and its bioequivalence was evaluated.Results LC-MS/MS methodologies were verified to meet the detection requirements.The main pharmacokinetic parameters of Venlafaxine test and reference preparations were as follows:T1/2,(7.16±2.34) and(6.95±1.57) h;Cmax,(522.89±201.12) and(515.22±159.29) ng/mL;Tmax,(10.38±1.69) and(10.50±2.07) h;AUC0-t,(8 398.64±3 332.86) and(8 050.71±2 103.15) ng·h/mL;AUC0-∞,(8701.60±3 303.29) and(8 450.01±2 273.45) ng·h/mL,respectively.The relative bioavailability of Venlafaxinewas(101.0±13.1)%.Conclusion Venlafaxine hydrochloride sustained-release tablets have bioequivalence with reference tablets in Beagle dogs.
引文
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[5]张志华,何周康,周彦彬,等.高效液相色谱-荧光法测定人血浆中文拉法辛及相对生物利用度[J].中南药学,2008,6(4):406-408.
[6]余勤,邹静,梁茂植,等.RP-HPLC法同时测定Beagle犬血浆中曲马多、文拉法辛和罗通定浓度[J].药物分析杂志,2008,28(4):532-536.
[7]陆川,贾晶莹,张梦琪,等.液相色谱串联质谱法测定人血浆中文拉法辛及其代谢物的浓度[J].中国新药与临床杂志,2011,8(30):634-638.
[8]陈银霞,杜江波,张逸凡,等.中国男性健康志愿者口服去甲文拉法辛缓释片对映体选择性药动学研究[J].药学学报,2015,50(4):486-491.
[9]中国药典[S].一部.2010.
[2]王永军,任珊,王俊锋,等.盐酸文拉法辛缓释片的制备及其家犬体内药动学初步研究[J].中国新药杂志,2010,19(21):1991-1994,2000.
[3]余勤,梁茂植,向瑾,等.盐酸文拉法辛缓释片人体药动学和生物等效性研究[J].中国新药杂志,2007,16(20):1716-1720.
[4]姜云平,于波涛,张勤,等.盐酸文拉法辛胶囊的人体生物等效性[J].西南国防医药,2009,19(11):1081-1083.
[5]张志华,何周康,周彦彬,等.高效液相色谱-荧光法测定人血浆中文拉法辛及相对生物利用度[J].中南药学,2008,6(4):406-408.
[6]余勤,邹静,梁茂植,等.RP-HPLC法同时测定Beagle犬血浆中曲马多、文拉法辛和罗通定浓度[J].药物分析杂志,2008,28(4):532-536.
[7]陆川,贾晶莹,张梦琪,等.液相色谱串联质谱法测定人血浆中文拉法辛及其代谢物的浓度[J].中国新药与临床杂志,2011,8(30):634-638.
[8]陈银霞,杜江波,张逸凡,等.中国男性健康志愿者口服去甲文拉法辛缓释片对映体选择性药动学研究[J].药学学报,2015,50(4):486-491.
[9]中国药典[S].一部.2010.