Cimetidine decreases theophylline clearance.
Cimetidine decreases theophylline clearance.
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西咪替丁降低茶碱清除率。
DOI：
10.1164/arrd.1981.123.6.615
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Dorr,R
中科院分区：
文献类型：
--
作者：
Jackson,JE;Powell,JR;Wandell,M;Bentley,J;Dorr,R
本研究验证了西咪替丁降低茶碱清除率的假设。5名健康成人在西咪替丁治疗前后静脉注射氨茶碱（6 mg/kg）。西咪替丁（300 mg）口服给药，每6小时前2天和氨茶碱剂量后18小时。在每次氨茶碱给药前和给药后24小时内采集血浆样本，通过酶介导免疫测定技术测定茶碱浓度，西咪替丁显著降低茶碱清除率，平均降低39%（对照组为3.85 ± 0.27 L/h，西咪替丁治疗组为2.34 ± 0.23 L/h，p < 0.002）。表观分布容积无变化（p > 0.5），而消除速率常数显著降低，平均降低42%（对照组为0.091 ± 0.013 h-1，西咪替丁组为0.053 ± 0.007 h-1，p < 0.005）。这相当于消除半衰期平均延长73%（范围：50 - 97%）。西咪替丁可能通过对肝微粒体单加氧酶系统的相对非特异性抑制来减缓茶碱的消除。这种作用可能会导致血清茶碱浓度发生临床显著变化。
This study tested the hypothesis that cimetidine decreases theophylline clearance. Aminophylline (6 mg/kg) was administered intravenously both before and after cimetidine treatment in 5 healthy adults. Cimetidine (300 mg) was administered orally every 6 h for 2 days before and 18 h after the aminophylline dose. Plasma samples were collected before and for 24 h after each aminophylline dose, and theophylline concentrations were determined by an enzymemediated immunoassay technique.Cimetidine significantly decreased theophylline clearance, mean decrease, 39% (3.85 ± 0.27 L/h control versus 2.34 ± 0.23 L/h with cimetidine treatment, p < 0.002). The apparent volume of distribution was unchanged (p > 0.5), whereas the elimination rate constant was significantly decreased by a mean of 42% (control, 0.091 ± 0.013 h-1versus 0.053 ± 0.007 h1with cimetidine treatment, p < 0.005). This corresponded to an average increase in elimination half-life of 73% (range, 50 to 97%). Cimetidine probably slowed theophylline elimination by relatively nonspecific inhibition of the hepatic microsomal mono-oxygenase system. This effect may produce clinically significant changes in serum theophylline concentrations.