Somogyi A, Gugler R
Clin Pharmacokinet. 1983 Nov-Dec;8(6):463-95. doi: 10.2165/00003088-198308060-00001.
Cimetidine is the first histamine H2-receptor antagonist with wide clinical application. It is a weak base and a highly water-soluble compound which can be measured in biological fluids by a number of high-pressure liquid chromatographic methods. Following intravenous administration, the plasma concentration profile follows multicompartmental characteristics. The total systemic clearance is high (500 to 600 ml/min) and is mainly determined by renal clearance. The volume of distribution (Vd beta or Vdss) is of the order of 1 L/kg and this about equals bodyweight. Elimination half-life is approximately 2 hours. Following oral administration of cimetidine, 2 plasma concentration peaks are frequently observed, probably due to discontinuous absorption in the intestine. The absolute bioavailability in healthy subjects is about 60%. In patients with peptic ulcer disease, bioavailability is around 70%, but the variation is much greater than in healthy subjects. Absorption and clearance of cimetidine are linear after 200 and 800mg doses. Mean steady-state plasma concentrations on a standard 1000mg daily dose are 1.0 microgram/ml (range 0.64-1.64 micrograms/ml) and are reproducible after treatment periods of up to 2 years. When taken with food, the extent of absorption is unaltered, but a delay occurs and only 1 peak in the plasma concentration curve is apparent. Partial gastrectomy (Billroth I, II) causes an increase in systemic availability of cimetidine by an unclear mechanism. Distribution of cimetidine leads to extensive uptake into kidney, lung and muscle tissues. It distributes into the cerebrospinal fluid (CSF) at a ratio of 0.1 to 0.2 compared with plasma. The mean saliva to plasma ratio is 0.2 (range 0.1-0.55). Plasma protein binding is 20%, and there is no relevant effect of changes in binding on the pharmacokinetics of cimetidine. Uptake of cimetidine into red blood cells leads to concentrations equal to those in plasma. Between 50 and 80% of the dose administered intravenously is recovered in urine as unchanged cimetidine. This fraction is less after oral doses, but is independent of the amount of the dose. In ulcer patients, 40% is recovered unchanged in urine after oral administration. Biliary excretion of cimetidine accounts for only 2% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)
西咪替丁是首个临床应用广泛的组胺H2受体拮抗剂。它是一种弱碱，是高度水溶性化合物，可用多种高压液相色谱法在生物体液中进行测定。静脉给药后，血浆浓度曲线呈现多室特征。全身总清除率较高（500至600毫升/分钟），主要由肾清除率决定。分布容积（Vdβ或Vdss）约为1升/千克，这大约等于体重。消除半衰期约为2小时。口服西咪替丁后，常观察到两个血浆浓度峰值，这可能是由于在肠道中吸收不连续所致。健康受试者中的绝对生物利用度约为60%。在消化性溃疡病患者中，生物利用度约为70%，但变化比健康受试者大得多。200毫克和800毫克剂量后，西咪替丁的吸收和清除呈线性。标准每日1000毫克剂量时的平均稳态血浆浓度为1.0微克/毫升（范围为0.64 - 1.64微克/毫升），在长达2年的治疗期后可重现。与食物同服时，吸收程度不变，但会出现延迟，血浆浓度曲线中仅出现1个峰值。部分胃切除术（毕罗一世、二世）通过不明机制导致西咪替丁的全身可用性增加。西咪替丁的分布导致其大量摄取到肾脏、肺和肌肉组织中。与血浆相比，它以0.1至0.2的比例分布到脑脊液（CSF）中。唾液与血浆的平均比值为0.2（范围为0.1 - 0.55）。血浆蛋白结合率为20%，结合变化对西咪替丁的药代动力学无相关影响。西咪替丁摄取到红细胞中导致其浓度与血浆中的浓度相等。静脉给药剂量的50%至80%以未改变的西咪替丁形式在尿液中回收。口服剂量后该比例较低，但与剂量大小无关。在溃疡患者中，口服给药后40%以未改变的形式在尿液中回收。西咪替丁的胆汁排泄仅占剂量的2%。（摘要截取自400字）
