Pharmacokinetics of famotidine in patients with cirrhosis and ascites

Summary The pharmacokinetics of famotidine has been investigated in ascitic cirrhotic patients. 10 decompensated cirrhotic patients were studied (9 m, 1 f), who had normal renal function, and six healthy control subjects (4 m, 2 f), matched for age, sex and weight. Each subject received on two occasions, at least four days apart, a single oral (40 mg) or intravenous dose (20 mg) of famotidine, at 21.00 h in a randomised manner. Serial blood samples were collected and famotidine in plasma was determined by a HPLC/UV method. Plasma data were subjected to non compartmental pharmacokinetic analysis.There were no statistically significant differences in pharmacokinetic parameters between the two groups after either the intravenous or oral administration of famotidine.The findings suggest that the dose of famotidine may not require any adjustment in ascitic patients without renal failure.     

法莫替丁咀嚼片的反相高效液相色谱法测定

目的 :建立法莫替丁咀嚼片含量测定的RP HPLC。方法 :采用ShimpackODS柱 (1 50mm× 6mm ,5μm) ,流动相为 :0 .1 %三乙胺的 0 .1mol·L- 1 乙酸钠溶液 (pH6 .0 0 )∶乙腈 (92∶8) ;流速 1 .0ml·min- 1 ,检测波长 2 66nm。结果 :在选定的色谱条件下 ,法莫替丁与有关物质完全分离 ;制剂中辅料对主药无干扰 ,法莫替丁在 5～ 2 0 0 μg·ml- 1 浓度范围内 ,峰面积与浓度线性关系良好 ,相关系数r =0 .9999,平均回收率为 99.4% ,RSD =0 .9%。结论 :本方法可用于法莫替丁咀嚼片的含量测定和有关物质检查。     

法莫替丁肠溶片的血浓度测定及其在人体的药代动力学研究

目的研究法莫替丁的血药浓度测定方法,并应用其进行法莫替丁片剂的人体药代动力学研究。方法采用固相萃取—高效液相色谱(HPLC)紫外检测法测定法莫替丁的血药浓度。18名健康男性志愿者,单剂量口服40mg法莫替丁片剂,不同时间点取静脉血,由血药浓度数据计算各自的主要药代动力学参数。结果所建立的血药浓度测定法能满足药代动力学实验要求。单次服用40mg法莫替丁片剂的主要药代动力学参数血药浓度-时间曲线下面积(AUC)0→12、AUC0→∞、Cmax、Tmax、T1/2分别为(882±185)、(912±187)ng·ml-1·h-1、(171±33)ng/ml、(2.3±0.4)和(2.6±2.7)h。结论法莫替丁的血药浓度测定方法简单、可靠。所得的药代动力学参数与国内外文献报道相似。     

复方法莫替丁咀嚼片治疗胃酸相关性症状的临床观察

目的：评价复方法莫替丁咀嚼片治疗胃酸相关性症状的有效性和安全性。方法：采用随机双盲对照试验，60例患者分别给予复方法莫替丁咀嚼片或法莫替丁片，20mg，bid，疗程14d。结果：两组的总有效率无统计学差异。各临床症状评分在治疗后均有显著下降，但两组间差异无统计学意义。除反酸症状的完全缓解时间，法莫替丁组优于复方法莫替丁咀嚼片组外，其他症状的完全缓解时间，两组间差异无统计学意义。两组均无严重不良反应。结论：复方法莫替丁咀嚼片是治疗胃酸相关性症状安全有效的药物。     

Risk factors for the development of gastric mucosal lesions in rheumatoid arthritis patients receiving long-term nonsteroidal anti-inflammatory drug therapy and the efficacy of famotidine obtained from the FORCE study

Abstract

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury, and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.     

Synergistic action of famotidine and chlorpheniramine on acetic acid-induced chronic gastric ulcer in rats

AIM: To assess the synergistic action of famotidine (FMD) and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats. METHODS: Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n=8), control group (n=8), FMD group (n = 8), CPA group (n=8), and FMD+CPA group (n=8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenation was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGFia) and IL-8 were determined by radioimmunoassay. RESULTS: The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGFia and MPO were confirmed. The effect of FMD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm2) was reduced from 40.18±2.6 in control group to 6.83±2.97 in PMD+CPA group, P<0.01, and from 32.9±3.27 in FMD group to 6.83±2.97 in PMD+CPA group, P<0.01. The plasma levels of IL-8 decreased from 0.69±0.11 ng/L in control group to 0.4±0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51±0.08 ng/L in FMD group to 0.4±0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGFia increased from 7.55±1.65 ng/L in control group to 16.62±0.97 ng/L in PMD+CPA group, P<0.01, and from 13.15±1.48 ng/L in FMD group to 16.62±0.97 ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12±2.05 u/L in control group to 4.33±0.95 u/L in PMD+CPA group, P<0.01, and from 8.3±1.29 u/L in FMD group to 4.33±0.95 u/L, P<0.01. CONCLUSION: The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the healing of ulcer.     

The growth capacity of hematopoietic progenitor cells in severe neutropenia induced by famotidine

Summary In four cases of severe neutropenia of unknown origin we found a strong inhibition of the growth of granulocyte-macrophage (GM) progenitor cells. The development of GM colonies in culture (GM-CFU-c) was more than 80% reduced in comparison to the control group. In particular, the interleukin 3- (IL-3) and granulocyte macrophage colony-stimulating factor-(GM-CSF) dependent growth was affected; a combination of growth factors (IL-3, GM-CSF, and G-CSF, the granulocyte colony-stimulating factor) resulted in a less reduced growth. The findings were primarily compatible with drug-induced bone marrow failure. Among the medications given to the patients, famotidine, an H2-receptor blocker, was discussed as an agent which possibly triggers off this process. After the withdrawal of famotidine, in three cases a continual increase of the growth of GM precursors was detected, reaching the normal level 7–17 days later. In one case, further investigations of the progenitor cells could not be carried out due to the death of the patient, but the rapid increase of neutrophils in the peripheral blood after withdrawal of famotidine pointed to the recovery of hematopoiesis. In vitro studies showed that famotidine, depending on the dose, inhibits the single growth factor-dependent colony growth (IL-3, GM-CSF, or G-CSF) of bone marrow progenitors from a concentration as low as 10g/ml. With the combination of all three growth factors only slight inhibitory effects were detectable (up to 150g/ml famotidine). These results indicate that famotidine, in common with other H2-receptor antagonists, can affect hematopoietic progenitor cells. However, the plasma concentration of famotidine normally used in ulcer therapy does not seem to influence the hematopoiesis. Apparently, the progenitor cells of only a few patients possess a higher sensitivity to the blockade of H2-receptors at this concentration of famotidine. This was demonstrated in one case (patient 3) 2 years after the patient had recovered from famotidine-induced neutropenia. The growth of peripheral myeloid, erythroid, and multilineage progenitor cells of this patient was remarkably reduced even at famotidine concentrations of 0.1–5.0g/ml whereas in the control group no inhibition was detected at these famotidine concentrations. Again, the IL-3-dependent colony formation was more affected than in the case of the combination of IL-3, GM-CSF, and G-CSF. After the removal of accessory cells the inhibitory effect of famotidine persisted, demonstrating that accessory cells do not play a major role in this process.     

法莫替丁葡萄糖注射液的制备工艺研究

目的:获得优化的法莫替丁葡萄糖注射液处方与制备工艺.方法:通过考察注射液的性状、颜色、pH以及主药、辅药的降解情况,获得处方的组成以及生产工艺.结果:通过试验研究,获得了优选的法莫替丁葡萄糖注射液的处方与制备工艺.结论:筛选得到的法莫替丁葡萄糖注射液处方合理,制备工艺可行,适合于工业化大生产.     

用HPLC法检查法莫替丁氯化钠注射液有关物质时的问题和讨论

目的：用新建HPLC法考察了6个厂家18批法莫替丁氯化钠注射液中的有关物质。方法：采用Agilent Zorbax SB-C18柱，（4．6mm×250mm,5μm）；A相（0．1％二氟乙酸）-B相（乙腈）为流动相；流速：1．0mL·min^-1；梯度洗脱；检测波长为254nm；柱温为室温；结果：用本文新建方法和国家药品标准方法分别对18批样品有关物质检查结果进行了比较，结果前者检查有关物质检查总量比后者高约2％～6％。结论：本法简便、准确、专属性好，灵敏度高，可用于法莫替丁氯化钠注射液中有关物质的检查。     

高效液相色谱法测定法莫替丁分散片的溶出度

目的建立法莫替丁分散片溶出度的HPLC测定方法。方法色谱柱为DiamondC18柱;流动相为庚烷磺酸钠溶液(取庚烷磺酸钠2.0g,加900ml溶解后,用冰醋酸调节pH值为3.9,加水至1000ml)-乙腈-甲醇(25∶6∶1),流速为1.0ml/min,检测波长为254nm。结果法莫替丁在10.56~24.64μg/ml范围内呈良好线性关系,r=0.9998,平均回收率99.6%,RSD=0.34%。结论方法准确可靠,简单易行,可用于该制剂的质量控制。