摘要
目的 研究氯沙坦及其代谢产物2-丁基-4-氯-1-[[2’-(1H-四唑-5-基）[1，1‘-联苯基]-4-基]甲基]-lH一咪唑-5-羧酸（E-3174）在中国汉族健康受试者体内的药动学。方法 10名健康受试者，男女各半，口服氯沙坦钾片50 mg，定时采血，用HPLC荧光法测定氯沙坦及其代谢物E-3174血药浓度，DAS2.0软件程序进行数据处理并采用SPSS13.0软件进行统计学分析。结果 氯沙坦和E-3174的主要药动学参数如下：ρmax分别为( 351±167)，( 241±60) μg·L-1; tmax分别为(1.35±1.06)，(3.60±1.68) h；t1/2分别为(0.82±0.40)，(4.66±1.10) h；AUC0-24分别为(498±172)，(1 853±194) μg ·h·L-1；AUC0-∞分别为(523±184)，(1 960±182) μg ·h·L-1。结论 氯沙坦及其代谢物E-3174的药动学特征和参数在个体间存在较大差异，临床治疗中应实行个体化给药方案。
Abstract
OBJECTIVE To investigate the pharmacokinetics of losartan and its major metabolite， E-3174， in Chinese Han healthy volunteers. METHODS Ten healthy volunteers (5 male and 5 female) were given 50 mg losartan potassium tablets. Blood samples were taken at predetermined time. The concentrations of losartan and E-3174 in plasma were determined by HPLC-fluorescence(FLU) method. The pharmacokinetic parameters were calculated by DAS2.0 software and compared by SPSS13.0 software. RESULTS The pharmacokinetic parameters of losartan and E-3174 were as follows: ρmax ( 351±167) and ( 241±60) μg·L-1, tmax (1.35±1.06) and （3.60±1.68）h, t 1/2 (0.82±0.40) and (4.66±1.10) h, AUC0-24 （498±172） and （1 853±194）μg ·h·L-1, AUC0-∞ (523±184) and (1 960±182) μg ·h·L-1. CONCLUSION The pharmacokinetic characteristics and parameters of losartan and E-3174 had significant inter-individual variability. Individual dose regimens should be used in the clinical treatment.
关键词
氯沙坦 /
E-3174 /
药动学 /
高效液相色谱-荧光检测法 /
汉族人
{{custom_keyword}} /
Key words
losartan /
E-3174 /
pharmacokinetics /
HPLC-FLU /
Chinese Han
{{custom_keyword}} /
郭涛 杨璐 夏东亚 唐云彪 颜鸣.
氯沙坦及其代谢物在汉族健康人体内药动学研究[J]. 中国药学杂志, 2010, 45(16): 1259-1261
GUO To;YNG Lu;XI Dong-y;TNG Yun-io;YN Ming.
Pharmacokinetics of Losartan and Its Metabolite in Han Healthy Volunteers[J]. Chinese Pharmaceutical Journal, 2010, 45(16): 1259-1261
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] YUAN Y， LIU X L， GUO X， et al. Bioequivalence of losartan capsules in healthy Chinese male volunteers [J]. Cent South Pharm（中南药学），2007，5(5)：467-470.
[2] ALAIN M， YVES C， JURG N， et al.Drug concentration response relationship in normal volunteers after oral administration of losartan， an angiotensin Ⅱ receptor antagonist[J].Clin Pharmacol Ther，1992， 51(5): 513-521.
[3] ANDREA S， HILDEGARD S L， EMST M. HPLC Assays to simultaneously determine the angiotensin-AT1 antagonist losartan as well as its main and active metabolite EXP 3174 in biological material of humans and rats[J]. J Pharm Biomed Anal， 1998， 16(5): 863-873.
[4] FARTHING D， SICA D， FAKHRY I， et al . Simple high - performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma ， urine and dialysate [J]. J Chromatogr B， 1997 ， 704(1-2): 374-378.
[5] MICHAEL A R， CHRISTINE I F， MAN W L. An improved method for the simultaneous determination of losartan and its major metabolite， EXP3174， in human plasma and urine by high-performance liquid chromatography with fluorescence detection[J]. J Pharm Biomed Anal， 1997， 15(7):1021-1029.
[6] TAKASHI I， TERUKAZU T， KEN I H， et al. Method for the simultaneous determination of losartan and its major metabolite， EXP-3174， in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry[J]. J Chromatogr B， 1999，734(2):325-330.
[7] YANG P， WANG Y J， LI L， et al. Bioequivalence of losartan capsule and tablet in healthy volunteers [J].Clin J Clin Phamacol（中国临床药理学杂志）， 2006， 22(6):436-439.
[8] MICHAEL A， RITTER， CHRISTINE I， et al.An improved method for the simultaneous determination of losartan and its major metabolite， EXP3174， in human plasma and urine by high-performance liquid chromatographic with fluorescence detection[J]. J Pharm Biomed Anal， 1997， 15(7):1021-1029.
[9] DON F， DOMENNIC S， ITAF F， et al.Simple high-performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma， urine and dialydate[J]. J Chromatogr B， 1997， 704(1-2):374-378.
[10] WU P B，CHEN Z L，XU W，et al.Study on CYP2C9 gene polymorphism and rational drug use[J]. J China Pharm（中国药房），2007，18(29)：2308-2309.
[11] HUANG M，WANG H，PING J，et al. Genetic polymorphism of human CYP3A4 gene in population of Han nationality in China [J]. Chin J Clin Pharmacol Ther(中国临床药理学与治疗学)，2005，11(3)：300-304.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(870 KB)
