Non-steroidal anti-inflammatory drugs that cause relatively little gastric damage

被引:3
作者
Tavares, IA [1 ]
Bennett, A [1 ]
机构
[1] Univ London Kings Coll, Sch Med & Dent, Rayne Inst, Acad Dept Surg, London SE5 9NU, England
关键词
acemetacin; COX-1; COX-2; human gastric mucosa; leucocytes; nimesulide;
D O I
10.1046/j.1440-1746.1998.01731.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Gastrointestinal damage by non-steroidal anti-inflammatory drugs (NSAID), which is common and sometimes fatal, involves inhibition of prostaglandin (PG) synthesis. The damage is less with NSAID that inhibit inflammatory cyclo-oxygenase (COX)-2 but not gastroprotective COX-1. We have compared nimesulide and acemetacin, two NSAID that cause relatively little gastric damage, with indomethacin for effects on purified COX-1 and COX-2. The results are related to findings on human gastric mucosa and leucocytes. With purified COX-1, inhibition was absent with nimesulide, weak with acemetacin (inhibitory concentration of 50% [IC50] 85 mu mol/L), and potent with indomethacin (IC50 0.6 mu mol/L). Inhibition of purified COX-2 occurred with nimesulide and indomethacin (IC50 values 90 and 4.1 mu mol/L, respectively) but not acemetacin. All results with nimesulide are consistent with a preferential block of COX-2 that contributes to relatively little gastric damage in patients. However, our previous report on acemetacin needs re-evaluation. Acemetacin did not inhibit sheep COX-2 and only weakly inhibited COX-1. Our previous leucocyte (COX-2) experiments required 24 h incubation, and hydrolysis of acemetacin to indomethacin presumably accounted for the COX-2 inhibition. In the few minutes of enzyme incubation, virtually no hydrolysis would be expected. Acemetacin itself presumably causes relatively little gastric damage mainly because it only weakly inhibits COX -1.
引用
收藏
页码:S190 / S192
页数:3
相关论文
共 17 条
[1]   NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND LIFE THREATENING COMPLICATIONS OF PEPTIC-ULCERATION [J].
ARMSTRONG, CP ;
BLOWER, AL .
GUT, 1987, 28 (05) :527-532
[2]  
BARRIER CH, 1989, ARTHRITIS RHEUM, V32, P926
[3]  
BEARDON PHG, 1989, Q J MED, V71, P497
[4]   NSAIDS, COX-2 INHIBITORS, AND THE GUT [J].
BENNETT, A ;
TAVARES, IA .
LANCET, 1995, 346 (8982) :1105-1105
[5]  
BENNETT A, 1993, DRUGS, V46, P1
[6]  
Bennett P., 1996, IMPROVED NON STEROID, P167
[7]   A FRAMEWORK FOR THE HISTORY OF ECONOMIC-GROWTH IN SOUTHEAST-ASIA [J].
JONES, EL .
AUSTRALIAN ECONOMIC HISTORY REVIEW, 1991, 31 (01) :5-19
[8]  
LAWS D, 1994, BR J CLIN RES, V5, P55
[9]  
LEE SH, 1992, J BIOL CHEM, V267, P25934
[10]   Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice [J].
Mizuno, H ;
Sakamoto, C ;
Matsuda, K ;
Wada, K ;
Uchida, T ;
Noguchi, H ;
Akamatsu, T ;
Kasuga, M .
GASTROENTEROLOGY, 1997, 112 (02) :387-397