地尔硫对人体内安替比林代谢的选择性抑制作用研究  

The selective inhibition of diltiazem on antipyrine metalboism in human

作　　者：印绮平[1,2] 奚念朱[1,2] 王宏图[1,2] 张静华 

机构地区：[1]上海医科大学华山医院临床药学研究室 [2]上海医科大学药学院生物药剂研究室

出　　处：《中国药学杂志》1999年第4期253-255,共3页Chinese Pharmaceutical Journal

摘　　要：目的：研究钙离子拮抗剂地尔硫（ＤＺ）对模型药安替比林（ＡＰ）在人体内代谢的选择性抑制作用。方法：６名健康男性志愿者，随机分成二组，分别ｐｏ单剂量ＡＰ８００ｍｇ及加服ＤＺ（３０ｍｇ，ｔｉｄ），６ｄ，取血并留尿４８ｈ，间隔２周后交叉给药。ＨＰＬＣ法测定血浆ＡＰ浓度和尿液中ＡＰ、３羟甲基安替比林（３ＯＨＭＡＰ）、４羟基安替比林（４ＯＨＡＰ）、Ｎ去甲基安替比林（ＮｏｒＡＰ）的浓度。结果：加服ＤＺ后，ＡＰｔ１／２（Ｋｅ）从（１３．７９±３．１７）ｈ延长至（１８．５４±３．１４）ｈ（Ｐ＜０．０１），Ｃｌｓ从（４０．４２±７．６２）ｍｌ·ｍｉｎ－１减少至（２８．６４±５．８４）ｍｌ·ｍｉｎ－１（Ｐ＜０．０１），ｃｍａｘ和ＡＵＣ明显增加（Ｐ＜０．０５）。４ＯＨＡＰ尿清除率从（１２．９１±３．４０）ｍｌ·ｍｉｎ－１减少至（３．５０±０．７８）ｍｌ·ｍｉｎ－１（Ｐ＜０．０１），３ＯＨＭＡＰ和ＮｏｒＡＰ的尿清除率没有明显变化。结论：ＤＺ选择性地抑制了ＡＰ在人体肝脏中的４羟基化代谢途径，提示ＤＺ是一作用较强的、选择性的肝药酶抑制剂。OBJECTIVE:To study the selective inhibitory effect of diltiazem(DZ) on hepatic drug metabolism by using antipyrine(AP) as a model drug.METHOD:Six healthy male subjects were divided into two groups in a randomized,crossover way.Each subject received orally AP 800mg after the administration of DZ (30mg,tid) for 6d or without DZ pretreatment with a two week wash out.Plasma and urine samples were collected until 48h.A simple HPLC method was used to determine AP and its main metabolites in plasma and urine.RESULTS:DZ treatment decreased AP clearance from (2.43±0.46) L·h -1 to (1.72±0.35)L·h -1 ( P <0.01),resulting in the prolongation of AP half life from (13.79±3.17)h to (18.54±3.14)h( P <0.01).During DZ treatment,fractional clearance of urinary 4 hydroxyantipyrine was decreased significantly from (12.91±3.40)ml·min -1 to (3.50±0.78)ml·min -1 ,with no significant change in 3 hydroxymethylantipyrine and norantipyrine.CONCLUSION:DZ inhibited the 4 hydroxytative metabolic pathway of AP,suggesting DZ may be a potent and selective microsomal enzyme inhibitor.

关 键 词：地尔硫ZHUO 安替比林 肝药酶抑制剂 选择性抑制 

分 类 号：R972.2[医药卫生—药品] R969.1[医药卫生—药学]