Cimetidine versus famotidine: the effect on the pharmacokinetics of theophylline in rats

The effects of cimetidine and a new, potent H2-antagonist, famotidine, on the single dose pharmacokinetics of theophylline were examined in rats. Male Sprague-Dawley rats (6 rats/group) received an i.v. dose of theophylline (6 mg/kg) alone and in conjunction with an i.v. dose of famotidine (10 mg/kg) or cimetidine (10 mg/kg). Venous blood samples were collected serially for seven hours after theophylline infusion and analyzed for theophylline concentration by HPLC. Concomitant famotidine administration did not alter any of the pharmacokinetic parameters of theophylline (AUC0- infinity; 38.1 +/- 8.7 vs. 38.8 +/- 6.3 micrograms.hr.ml-1), while cimetidine demonstrated a significant reduction in theophylline systemic clearance (0.11 +/- 0.02 vs. 0.16 +/- 0.02 L/hr/kg; p less than 0.001), a 40% prolongation of half-life (2.8 +/- 0.9 vs. 2.0 +/- 0.5 hr), with no change in the volume of distribution (0.39 +/- 0.1 vs. 0.41 +/- 0.13 L/kg). These results suggest that in contrast to cimetidine, famotidine, a non-imidazole H2-receptor antagonist, does not interfere with theophylline disposition in the rat.     

RP-HPLC法测定西咪替丁片中西咪替丁的含量

目的:改进西咪替丁片中西咪替丁含量的测定方法。方法:采用反相高效液相色谱法。色谱柱为shimadzuVP-ODSC18柱,流动相为磷酸氢二钠溶液-甲醇(60∶40),流速为1.0mL·min-1,检测波长为215nm,进样量为10μL,柱温为30℃。结果:西咪替丁进样量在0.38～1.31μg(r=0.9999)范围内与峰面积积分值呈良好的线性关系;平均加样回收率为99.9%,RSD=0.54%(n=6)。结论:该方法简单,结果准确、可靠,可用于西咪替丁片的质量控制。     

Synthesis of Cimetidine

A simple and economical synthesis of cimetidine is described. It is based on the reaction of 4-halomethyl-5-methylimidazole with N-cyano-N′-methyl-N″-(2-mercaptoethyl)guanidine in water-ethanol at pH 9.0 ± 0.3. Pure crystalline cimetidine is obtained in about 75% yield.     

西咪替丁的晶型研究

目的：建立西咪替丁晶型的测定方法,并对国内西咪替丁原料的晶型进行考察：方法：差示扫描量热（DSC）法,红外光谱法（IR）及X射线衍射（X－ray)法。结果：国内不同厂家生产的西咪替丁原料晶型不同,有A晶型,B晶型和混合晶型。结论：西咪替丁晶型可以采用DSC法,IR法及X－ray法测定,DSC法简便易行且可进行粗略定量。     

Cimetidine interaction with amitriptyline

Summary The interaction of cimetidine with amitriptyline was assessed by means of amitriptyline and nortriptyline plasma concentration measurements, standing blood pressure and pulse rate, digit symbol substitution, and visual analogue scales. Cimetidine increased plasma amitriptyline concentrations and decreased plasma nortriptyline concentrations, apparently by inhibiting presystemic metabolism. The changes in blood pressure, pulse rate and digit symbol substitution correlated with changes in concentrations of amitriptyline in plasma and expected changes based on a dose ranging preliminary experiment. Changes in subjective ratings of effects correlated with changes in nortriptyline concentrations in plasma.     

Long-term Follow-up Study of Cimetidine

In a 5-year follow-up study of 8553 recipients of cimetidine at Group Health Cooperative of Puget Sound, we examined the frequency of uncommon serious illness requiring hospitalization that may have been drug induced. With the possible exception of one patient with probable drug-induced liver disease, we did not find any instances of serious illness requiring hospitalization that could be attributed with reasonable certainty to cimetidine. This large study provides reassurance that cimetidine is a relatively safe medication.     

HPLC测定西咪替丁胶囊的含量

目的 建立西咪替丁胶囊的含量测定方法.方法 采用Waters高效液相色谱仪,TIANHE C18柱 (250 mm ×4.6 mm,10 μm),0.05 mol·L-1磷酸二氢钾溶液(三乙胺调节pH至5.8)-甲醇(210:300)为流动相,检测波长为219 nm测定西咪替丁胶囊的含量.结果 使用高效液相色谱法可以准确有效地测定西咪替丁胶囊的含量.结论 该方法在5～50 μg·ml-1的浓度范围内线性关系良好(r=0.9999,n=6),平均回收率为100.3%,RSD=0.6%(n=6),方法简便,准确,适用于西咪替丁胶囊的含量测定.     

高效液相色谱法测定西咪替丁注射液的含量

目的 :建立用高效液相色谱法测定西米替丁注射液含量的方法。方法 :以甲硝唑为内标 ,色谱柱为ODSC18柱 ,甲醇 水 三乙胺 (2 7∶73∶0 1,用磷酸调节PH至 3 5± 0 1)为流动相 ,流速 0 8ml/min ,检测波长 2 2 5nm。结果 :在 5 0～ 30 0 μg·ml-1的浓度范围内具有良好的线性关系 ,r =0 9999,平均回收率为 10 0 3% ,RSD =0 4 %。与美国药典 2 3版方法相比 ,无显著性差异 (P >0 0 5 )。结论 :该方法简便、灵敏、准确可靠 ,适用于西米替丁注射液的含量测定。     

Cimetidine alters pethidine disposition in man

The effect of concurrent cimetidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (18-31 years). The subjects received 70 mg i.v. pethidine HCl doses before and during cimetidine treatment (1200 mg/day p.o.). During cimetidine treatment, pethidine total body clearance (CL) decreased by 22% (0.611 +/- 0.101 [mean +/- s.d.] to 0.474 +/- 0.098 1 kg-1 h, P less than 0.05) and pethidine volume of distribution at steady state (Vss) decreased by 13% (4.79 +/- 0.82 to 4.16 +/- 0.75 l/kg, P less than 0.05). A cimetidine-induced reduction in pethidine oxidation to norpethidine was suggested by a 23% reduction in norpethidine area under the curve from 0 to 24 h (472 +/- 93 to 362 +/- 38 ng ml-1 h, P less than 0.05) and a 29% reduction in peak norpethidine concentration (26.7 +/- 5.3 to 18.9 +/- 1.9 ng/ml, P less than 0.05). There were no significant linear correlations of serum trough cimetidine concentration with percentage reductions in pethidine CL, pethidine Vss, norpethidine AUC (24), or norpethidine peak concentrations. It would appear that the cimetidine-pethidine kinetic interaction may be of sufficient magnitude to be clinically significant. Caution is advised when patients are treated concurrently with these two agents.     

西咪替丁片的溶出度的研究

目的: 解决西咪替丁片在有效期内(2 a)溶出度不合格的问题.方法: 用正交试验法对西咪替丁片的生产工艺进行优化考察.结果: 经加速实验,3个月的溶出度为86.5%.结论: 经优化后的新工艺完全可行.     

Cimetidine and ranitidine in duodenal ulcer

Two histamine H2 antagonists, cimetidine and ranitidine, given in doses of 1 g daily and 200 mg daily to 18 and 20 patients respectively proved equivalent in promoting healing of duodenal ulcer. No adverse effects occurred during the trial, though serum urea and creatinine concentrations tended to rise slightly during treatment with cimetidine but not ranitidine. Choice between the two drugs is likely to be influenced by overall patterns of adverse effects rather than considerations of individual potency.     

Cimetidine impairs the elimination of chlormethiazole

Summary Cimetidine impairs the systemic clearance of a number of low extraction drugs and this study examines its effect on the oral clearance of the high extraction drug, chlormethiazole. Cimetidine (1 g/day for 7 days) caused the clearance of chlormethiazole to fall to 69% of pretreatment values. It also prolonged the elimination half-life by 60%. The findings indicate that the metabolism of chlormethiazole is inhibited by cimetidine and the co-administration of these drugs may lead to excess sedation and respiratory depression.