Okumura H, Nishimura E, Kariya S, Ohtani M, Uchino K, Fukatsu T, Odanaka J, Takahashi T, Watanabe K, Itoh T, Hashiguchi M, Echizen H, Rikihisa T
Department of Hospital Pharmacy, Tokyo Postal Services Agency Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo 102-8798, Japan.
Yakugaku Zasshi. 2001 Mar;121(3):253-7. doi: 10.1248/yakushi.121.253.
Persistent dry cough is well known as the most common side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the relationship between a cough and ACE gene polymorphism, plasma bradykinin (BK), substance P (SP) and ACE inhibitor concentrations in patients with hypertension or chronic nephritis. First, ACE genotyping was carried out in 96 patients, 42 with coughs and 54 without coughs, which had been treated with various kinds of ACE inhibitors. However, no significant difference in the ACE genotypes was observed between the two groups. Second, the plasma concentrations of BK, SP and ACE inhibitor were measured in 12 patients, which were treated with trandolapril at a daily dose of 1 mg for 4-33 weeks. In 3 patients, the cough was induced during the trandolapril therapy, while it was induced not in 9 patients. The plasma levels of BK and SP did not significantly change after trandolapril administration in the patients with and without coughs. Between the two groups, there were no significant differences in the plasma levels of BK and SP either before or after the trandolapril therapy. Also the plasma concentrations of trandolapril and trandolaprilat, the active metabolite of trandolapril, did not significantly differ between the two groups. These results suggest that there is no significant relationship between the ACE inhibitor-induced cough and ACE gene polymorphism, plasma BK, SP and ACE inhibitor concentrations in patients with hypertension or chronic nephritis.
持续性干咳是众所周知的血管紧张素转换酶(ACE)抑制剂最常见的副作用。我们研究了高血压或慢性肾炎患者咳嗽与ACE基因多态性、血浆缓激肽(BK)、P物质(SP)及ACE抑制剂浓度之间的关系。首先,对96例接受过各种ACE抑制剂治疗的患者进行了ACE基因分型,其中42例有咳嗽症状,54例无咳嗽症状。然而,两组之间在ACE基因型上未观察到显著差异。其次,对12例每日服用1mg群多普利治疗4 - 33周的患者测定了血浆BK、SP和ACE抑制剂的浓度。3例患者在群多普利治疗期间出现咳嗽,而9例患者未出现咳嗽。群多普利给药后,有咳嗽和无咳嗽患者的血浆BK和SP水平均无显著变化。群多普利治疗前后,两组之间的血浆BK和SP水平也无显著差异。此外,两组之间群多普利及其活性代谢产物群多普利拉的血浆浓度也无显著差异。这些结果表明,在高血压或慢性肾炎患者中,ACE抑制剂引起的咳嗽与ACE基因多态性、血浆BK、SP及ACE抑制剂浓度之间无显著关系。