两种烯丙孕素口服液在猪体内的比较药动学研究
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摘要
比较国产和进口烯丙孕素口服液在健康母猪体内的药物代谢动力学。将16头健康苏姜商品母猪随机分为2组,分别单剂量灌服国产烯丙孕素口服液和进口烯丙孕素口服液,按体重给药量均为1.0 mg/kg,进行药动学比较研究。给药后按预定时间采集血样,采用液相色谱-串联四级杆质谱法测定血浆中烯丙孕素含量,实测血药浓度-时间数据采用WINNONLIN 6.3版药动学分析软件处理。国产制剂和进口制剂的达峰时间(Tmax)分别为(0.81±0.14)h、(1.59±0.80)h;达峰浓度(Cmax)分别为(175.19±58.12)ng/m L、(100.47±19.64)ng/m L;消除半哀期(t1/2)分别为(3.89±0.75)h、(3.14±0.24)h;平均滞留时间(MRT0~t)分别为(5.05±0.36)h、(5.06±0.71)h;药时曲线下面积(AUC0-t)分别为(729.82±179.76)ng·h·m L-1、(554.56±156.55)ng·h·m L-1。国产烯丙孕素口服液的相对生物利用度为131.60%。国产烯丙孕素口服液Cmax显著高于进口烯丙孕素口服液,而其它参数t1/2、Tmax、AUC0-t、MRT0~t无显著性差异。研究表明,国产烯丙孕素口服液在母猪体内具有吸收好、消除快、生物利用度高等优点。
This study was to compare the pharmacokinetics of domestic and imported altrenogest oral liquids in healthy sows. Sixteen sows were divided into two groups with eight in each. The pigs in one group were administered with domestic altrenogest oral liquid at a single dose of 1. 0 mg/kg,and those in the other group were administered with imported altrenogest oral liquid also at a single dose of 1. 0 mg/kg. Then,blood samples were collected at different designed intervals after administration,and plasma concentrations of altrenogest were measured by HPLC-MS/MS. Finally,the concentration-time data of altrenogest was analyzed by WINNONLIN 6. 3. The main pharmacokinetic parameters obtained of the domestic and imported preparations were as follows: Tmaxwere( 0. 81± 0. 14) h and( 1. 59± 0. 80) h; Cmaxwere( 175. 19±58. 12) ng/m L and( 100. 47±19. 64) ng/m L; t1/2 were( 3. 89±0. 75) h and( 3. 14±0. 24) h; MRT0 ~ twere( 5. 05± 0. 36) h and( 5. 06±0. 71) h; AUC0-twere( 729. 82±179. 76) ng·h·m L-1 and( 554. 56± 156. 55) ng·h·m L-1,respectively. The relative bioavailability of domestic altrenogest oral liquid was 131. 60%. The domestic altrenogest oral liquid had a significantly higher Cmaxthan the imported one,but in the other pharmacokinetic parameters( AUC0-t,AUC0-∞,Tmax) there were no significant differences between the two altrenogest oral liquid( P>0. 05). Domestic altrenogest oral liquid had the advantages of good absorption,fast elimination and high bioavailability in sows.
This study was to compare the pharmacokinetics of domestic and imported altrenogest oral liquids in healthy sows. Sixteen sows were divided into two groups with eight in each. The pigs in one group were administered with domestic altrenogest oral liquid at a single dose of 1. 0 mg/kg,and those in the other group were administered with imported altrenogest oral liquid also at a single dose of 1. 0 mg/kg. Then,blood samples were collected at different designed intervals after administration,and plasma concentrations of altrenogest were measured by HPLC-MS/MS. Finally,the concentration-time data of altrenogest was analyzed by WINNONLIN 6. 3. The main pharmacokinetic parameters obtained of the domestic and imported preparations were as follows: Tmaxwere( 0. 81± 0. 14) h and( 1. 59± 0. 80) h; Cmaxwere( 175. 19±58. 12) ng/m L and( 100. 47±19. 64) ng/m L; t1/2 were( 3. 89±0. 75) h and( 3. 14±0. 24) h; MRT0 ~ twere( 5. 05± 0. 36) h and( 5. 06±0. 71) h; AUC0-twere( 729. 82±179. 76) ng·h·m L-1 and( 554. 56± 156. 55) ng·h·m L-1,respectively. The relative bioavailability of domestic altrenogest oral liquid was 131. 60%. The domestic altrenogest oral liquid had a significantly higher Cmaxthan the imported one,but in the other pharmacokinetic parameters( AUC0-t,AUC0-∞,Tmax) there were no significant differences between the two altrenogest oral liquid( P>0. 05). Domestic altrenogest oral liquid had the advantages of good absorption,fast elimination and high bioavailability in sows.
引文
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[10]DAN Zhang,JIN-A Park.Determination of residual levels of naloxone,yohimbine,thiophanate,and altrenogest in porcine muscle using Qu ECh ERS with liquidc romatography and triple quadrupole mass spectrometry[J].Research Article,2016(3):835-841.
[11]Matilda Lampinen-Salomonsson,Elin Beckman,Ulf Bondesson.Detection of altrenogest and its metabolites in post administration horse urine using liquid chromatography tandem mass spectrometry—increased sensitivity by chemical derivatisation of the glucuronic acid conjugate[J].J of Chromatography 2006,B,833:245-256.
[2]张贤群,Johannes Kauffold.利用烯丙孕素使授精未孕母猪重返预定的配种方案[J].国外畜牧兽医(猪与禽),2008,28(1):84-93.
[3]Sitrukware R.Pharmacokinetics profile of progestins[J].Maturitas,2004,47:277-283.
[4]Hogson D,Howe S,jeffcott L,et al.Effect of prolonged use of altrenogest on behaviour in mares[J].The Veterinary Journal,2005,169:113-115.
[5]Johnson N N,Brady HA,Whisnant CS.Effects of oral altrenogest on sexual and aggressive behaviours and seminal parameters in young stallions[J].J of Equine Vet Sci,2007,18:249-253.
[6]Kluber E F,Pollman D S,Davis D L.Body growth and testicular characteristics of boars fed a synthetic progestogen,altrenogest[J].J Anim Sci,1985,61:1441-1447.
[7]志强等.烯丙孕素对烯丙孕素对母猪早产和繁殖素对母猪早产和繁殖性能的影响[J].中国畜牧业,2012:86-87.
[8]M machnik I,Hegger M,Kietzmann M,etal.Pharmacokinetics ofaltrenogest in horses[J].J of Vet Pharmacol and Therapeutics.2007(1),30:86-90.
[9]Martina R,Eitharov A,Libor R.Development and validation of an LC-MS/MS method for the determination of six gestagens in kidney fats[J].Food Additives&Contaminants,2013(6):995-999.
[10]DAN Zhang,JIN-A Park.Determination of residual levels of naloxone,yohimbine,thiophanate,and altrenogest in porcine muscle using Qu ECh ERS with liquidc romatography and triple quadrupole mass spectrometry[J].Research Article,2016(3):835-841.
[11]Matilda Lampinen-Salomonsson,Elin Beckman,Ulf Bondesson.Detection of altrenogest and its metabolites in post administration horse urine using liquid chromatography tandem mass spectrometry—increased sensitivity by chemical derivatisation of the glucuronic acid conjugate[J].J of Chromatography 2006,B,833:245-256.