Famotidine, a new H2-receptor antagonist, does not affect hepatic elimination of diazepam or tubular secretion of procainamide
Famotidine, a new H2-receptor antagonist, does not affect hepatic elimination of diazepam or tubular secretion of procainamide
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法莫替丁是一种新型 H2 受体拮抗剂，不影响地西泮的肝脏消除或普鲁卡因酰胺的肾小管分泌
DOI：
10.1007/bf00607913
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发表时间：
2004
影响因子：
2.9
通讯作者：
B. Rosenkranz
中科院分区：
文献类型：
--
作者：
U. Klotz;P. Arvela;B. Rosenkranz
摘要
在一项随机交叉研究中，对8名健康男性志愿者在使用H₂受体拮抗剂法莫替丁预处理前后，单次给予地西泮和单次给予普鲁卡因胺的药效学反应进行了评估。还研究了地西泮和普鲁卡因胺的药代动力学，并测量了法莫替丁与人肝微粒体的结合情况。西咪替丁诱导的结合变化，其光谱解离常数（Ks）为0.87 mM，而法莫替丁在浓度高达4 mM时未产生可测量的光谱改变。法莫替丁未显著改变地西泮的消除半衰期（t₁/₂：45.6小时）和总血浆清除率（CL：0.28 ml/min/kg）（t₁/₂ = 39.0 ± 11.4小时；CL = 0.31 ± 0.08 ml/min/kg）。同样，法莫替丁也未增强地西泮的镇静作用。法莫替丁也未显著改变普鲁卡因胺和N - 乙酰普鲁卡因胺（NAPA）的药效学和药代动力学：在法莫替丁作用下，普鲁卡因胺t₁/₂为2.9小时对3.0小时，肾清除率（CLR）为436 ml/min对443 ml/min；在法莫替丁作用下，NAPA的CLR为195 ml/min对212 ml/min。数据表明，与西咪替丁不同，法莫替丁不影响地西泮（肝脏消除）或普鲁卡因胺（肾小管分泌）的药代动力学。这种新型H₂受体拮抗剂似乎对这两种药物消除类型都没有相互作用的可能性。
SummaryIn 8 healthy male volunteers the pharmacodynamic responses to a single dose of diazepam and a single dose of procainamide were assessed before and after pre-treatment with the H2-receptor antagonist famotidine in a randomized crossover study. The pharmacokinetics of diazepam and procainamide were also studied, and the binding of famotidine to human liver microsomes was also measured. Cimetidine induced binding changes with a spectral dissociation constant (Ks) of 0.87 mM, whereas famotidine produced no measurable spectral alteration in concentrations up to 4 mM. The elimination half-life (t1/2: 45.6 h) and total plasma clearance (CL: 0.28 ml/min/kg) of diazepam were not significantly altered by famotidine (t1/2=39.0±11.4 h; CL =0.31±0.08 ml/min/kg). Similarly, there was no enhancement of the sedative effect of diazepam by famotidine. The pharmacodynamics and pharmacokinetics of procainamide and N-acetylprocainamide (NAPA), too, were not significantly changed by famotidine: procainamide t1/2 2.9 vs 3.0 h under famotidine and renal clearance (CLR) 436 vs 443 ml/min; and NAPA CLR 195 vs 212 ml/min under famotidine. The data suggest that famotidine, in contrast to cimetidine, does not affect the pharmacokinetics of diazepam (hepatic elimination) or procainamide (tubular secretion). This new H2-receptor antagonist appears to be devoid of an interaction potential for either type of drug elimination.
西咪替丁对药物氧化（安比林和地西泮）与结合（对乙酰氨基酚和劳拉西泮）的不同影响：西咪替丁预防对乙酰氨基酚毒性。
DOI：
--
发表时间：
1983
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Abernethy,DR;Greenblatt,DJ;Divoll,M;Ameer,B;Shader,RI
通讯作者：
Shader,RI