Comparison of the Effects of Cimetidine and Ranitidine on the Pharmacokinetics of Disopyramide in Man

The widely prescribed antiulcer agents cimetidine and ranitidine have the potential to affect the absorption, metabolism or renal excretion of disopyramide. This study investigated the effect of a single oral dose of cimetidine or ranitidine on the pharmacokinetics of disopyramide and mono-N-dealkyldisopyramide in six healthy volunteers. The treatment was conducted in a randomized cross-over design. Serum levels and urinary recoveries of disopyramide and mono-N-dealkyldisopyramide were assayed by HPLC. Cimetidine significantly elevated the maximum plasma concentration of disopyramide, the area under the plasma concentration-time curve and the total amount of disopyramide excreted unchanged in the urine, but the serum profile of mono-N-dealkyldisopyramide was not significantly affected. The effects of ranitidine on the pharmacokinetics of disopyramide and mono-N-dealkyldisopyramide were not significant. The interaction between cimetidine and disopyramide occurred mainly at the site of absorption. The results indicate that cimetidine, but not ranitidine, significantly increased the absorption of orally administered disopyramide.     

Intestinal Uptake of Cimetidine and Ranitidine in Rats

The H₂-receptor antagonists exhibit unusual absorption behavior in that double peaks often occur after oral administration. Moreover, administration with some high potency antacids decreases the extent of absorption. To date, no explanation that can completely account for these observations has been advanced. One problem is that there is a lack of consensus as to the mechanism of absorption of the H₂-receptor antagonists from the gastrointestinal tract. In the studies reported here, the mechanism and regional dependence of intestinal uptake of two H₂-receptor antagonists, cimetidine and ranitidine, were investigated in rats using the in vitro everted ring technique. The uptake rate of cimetidine from both jejunum and colon was linear with concentration (in the range of 0.0005-40 mM), and there was no significant competition for uptake in the presence of the structurally similar H₂-receptor antagonists, famotidine and ranitidine. In the case of ranitidine too, the uptake rate from the jejunum and colon was linear with concentration (in the range of 0.0005-5 mM), and there was no competition for uptake by either famotidine or cimetidine. These data indicate that uptake of cimetidine and ranitidine in the rat jejunum and colon occurs by a predominantly passive process. Both cimetidine and ranitidine exhibited regional differences in uptake rate. Uptake tended to be greatest in the ileum, similar in duodenum and jejunum, and lowest in the colon. However, differences in uptake rates between locations in the small intestine appeared to be too modest to account for the double peak behavior of either compound.     

Effects of Sho-saiko-to on the Pharmacokinetics and Pharmacodynamics of Tolbutamide in Rats

Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese traditional medicine, is frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases, there is a dearth of information about interactions between sho-saiko-to and co-administered drugs. This paper reports the effects of Sho-saiko-to on the pharmacokinetics and glucose responses of a sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration in rats. After oral administration of tolbutamide (50 mg kg^?1) with or without Sho-saiko-to extract powder (300 mg kg^?1) to male Sprague-Dawley rats cannulated in the jugular vein, plasma tolbutamide and glucose levels were periodically measured. Co-administration of Sho-saiko-to tended to elevate the plasma tolbutamide concentration in the absorption phase. A two-compartment lag-time model was found to describe the plasma tolbutamide concentration-time data. The maximum concentration of tolbutamide was significantly increased and time to reach the maximum concentration was reduced to about 70% by co-administration with Sho-saiko-to. There was no significant change in area under the curve or in the elimination half-life of tolbutamide. The extent of the lowering effect of tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased after 5 h after co-administration of Sho-saiko-to. In conclusion, these studies suggest that sho-saiko-to slightly hastens the gastrointestinal absorption of tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration.     

奥美拉唑对奥拉西坦在大鼠体内药动学的影响研究

目的:研究奥美拉唑对奥拉西坦在大鼠体内药动学的影响。方法:检测大鼠先后灌胃给予奥美拉唑(4mg.kg-1,每日2次,连续7d)与奥拉西坦(200mg.kg-1)后12h内奥拉西坦的血药浓度,计算药动学参数,并与奥拉西坦单一给药大鼠的参数进行比210较n;m采,用柱高温效为液40相℃色,谱进法样检量测为,2色0μ谱L柱。为结S果ym:奥me拉try西s坦hie检dT测MR浓P1度8,流的动线相性为范乙围腈为-2水～(130.20:m96g..8)L,-流(1r速=为0.909.89m8)L.,最mi低n-检1,检测测限波为长0.0为1mg.L-1,绝对回收率为(91.1±5.17)%～(98.4±1.99)%,方法回收率为(96.35±3.01)%～(102.23±1.37)%;单用与联用的药动学参数分别为t1/2:(2.2±0.8)、(1.6±0.4)h,cmax:(51.1±23.1)、(41.4±7.9)mg.L-1,AUC0～12h:(242.1±86.0)、(177.1±38.3)mg.h.L-1,二者比较无显著性差异。结论:奥美拉唑对奥拉西坦在大鼠体内的药动学无显著性影响。     

法莫替丁、雷尼替丁、西米替丁的药理作用比较

Fam非竞争性地拮抗组胺对豚鼠心房和大鼠于官的作用.而Ran和Cim呈竞争性地拮抗作用。它们的pA_z值分别是6.24和8.26.5.16和7.22.4.08和6.17。Fam、Ran、Cim均呈剂量依赖性的减少大鼠基础胃酸和胃蛋白酶分泌,抑制组胺刺激性胃酸分泌.预防应激及消炎痛和组胺引起的急性胃粘膜损伤.促进醋酸所致的慢性胃溃疡的愈合.F am的作用强度为Ran的6～8 倍.Cim的30～40倍.此外Cim能明显增加戊巴比妥的催眠作用,Fam的作用弱于Cim·而Ran没有作用。     

Comparative Evaluation of the Hemodynamic Effects of Oral Cimetidine,Ranitidine, and Famotidine as Determined by Echocardiography

Study Objective . To evaluate the influence of cimetidine, ranitidine, famotidine, and placebo on cardiac performance as determined by echocardiography. Design . Randomized, four-way crossover trial. Setting . Echocardiography laboratory at a university hospital. Participants . Twelve healthy volunteers. Interventions . Volunteers received oral treatment with placebo, cimetidine 800 mg, ranitidine 300 mg, or famotidine 40 mg once/day for 7 days. Measurements and Main Results . On the seventh day of each study phase, 2 hours after administration of the final dose, each subject underwent cardiac echocardiography and Doppler flow studies. No significant differences were detected in ejection fraction, peak flow velocity, or percentage fractional shortening among the treatment phases. A large degree of variability in ejection fraction was observed, with some subjects experiencing marked decreases. Conclusion . The histamine-2 (H₂)-receptor antagonists had no effect on the hemodynamic variables as determined by echocardiography. The variability in the hemodynamic response may in part explain the conflicting results reported in the literature. It also raises the question as to whether certain individuals are more sensitive to the potential cardiac effects of H₂-receptor antagonists.     

The Effect of Cimetidine and Ranitidine Administration With Zidovudine

Study Objective . To evaluate the possibility of a drug interaction with zidovudine and histamine₂-receptor antagonists in individuals infected with the human immunodeficiency virus. Design . Randomized crossover study. Setting . University-affiliated research center. Patients . Six HIV-infected individuals. Interventions . The subjects received 7-day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1200 mg/day, and zidovudine with ranitidine 300 mg/day. Measurements and Main Results . The renal clearance of zidovudine when given alone was 0.41 L/kg/hour, and was reduced to 0.18 L/kg/hour (p=0.002) when given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 μM (p=0.01), the urinary ratio of metabolite to parent increased from 5.16 to 9.96 (p=0.0001), and the fraction of zidovudine converted to metabolite increased from 0.86 to 0.92 (p=0.0025). Conclusion . Cimetidine presumably inhibits the renal clearance of zidovudine by competing for tubular secretion. Based on the observation that neither cimetidine nor ranitidine had a significant effect on serum concentrations of zidovudine or zidovudine glucuronide, a change in the dosage of zidovudine is not warranted.     

奥美拉唑和雷尼替丁治疗消化性溃疡的系统评价

目的:评价奥美拉唑和雷尼替丁在治疗消化性溃疡方面的疗效和不良反应。方法:电子检索中文科技期刊数据库、万方数据库。采用Revan5.0软件进行Meta分析,对可合并分析资料无异质性者使用固定效应模型,有异质性者分析异质性产生原因,并使用敏感性分析或亚组分析处理,若仍无法消除异质性,采用随机效应模型合并分析。结果:奥美拉唑与雷尼替丁治疗消化性溃疡的总有效率,差异有统计学意义[P<0.05,OR=3.96,95%C(I2.57,6.11)];奥美拉唑的不良反应远低于雷尼替丁。结论:Meta结果显示,奥美拉唑治疗消化性溃疡明显优于雷尼替丁。     

奥美拉唑肠溶胶囊的人体药动学及生物等效性

目的:建立测定奥美拉唑血药浓度的高效液相色谱法,并考察奥美拉唑肠溶胶囊人体药动学和比较两种制剂的生物等效性。方法:采用两周期两制剂交叉试验设计,24例男性健康志愿者随机分为两组,分别单剂量交叉口服奥美拉唑肠溶胶囊(受试试剂)和洛赛克肠溶胶囊(参比制剂)40 mg,以反相高效液相法测定给药后不同时间点奥美拉唑血药浓度,采用DAS房室模型法和生物等效性计算程序进行统计分析。结果:奥美拉唑肠溶胶囊(受试试剂)和洛赛克肠溶胶囊(参比制剂)血药浓度-时间曲线符合一室开放模型。主要药动学参数:tmax分别为(1．94±0．86)h和(2．11±0．73)h,Cmax分别为(796．57±336．63)ng·ml-1和(776．30±341．55)ng·ml-1,AUC0→∞分别为(1755．86±1169．44)ng·h·ml-1和(1749．90±1241．7)ng·h·ml-1。受试制剂对参比制剂的相对生物利用度为(105．00±30．08)％。结论:两种制剂具有生物等效性。     

Human Jejunal Permeability of Two Polar Drugs: Cimetidine and Ranitidine

PURPOSE: To determine the human jejunal permeability of cimetidine and ranitidine using a regional jejunal perfusion approach, and to integrate such determinations with previous efforts to establish a baseline correlation between permeability and fraction dose absorbed in humans for soluble drugs. METHODS: A sterile multi-channel perfusion tube, Loc-I-Gut, was inserted orally and positioned in the proximal region of the jejunum. A solution containing cimetidine or ranitidine and phenylalanine, propranolol, PEG 400, and PEG 4000 was perfused through a 10 cm jejunal segment in 6 and 8 subjects, respectively. RESULTS: The mean Peff (+/- se) of cimetidine and ranitidine averaged over both phases were 0.30 (0.045) and 0.27 (0.062) x 10(-4) cm/s, respectively, and the differences between the two were found to be statistically insignificant. The mean permeabilities for propranolol, phenylalanine, and PEG 400 averaged over both phases and studies were 3.88 (0.72), 3.36 (0.50), and 0.56 (0.08) x 10(-4) cm/s, respectively. The differences in permeability for a given marker were not significant between phases or between the two studies. CONCLUSIONS: The 10-fold lower permeabilities found for cimetidine and ranitidine in this study, compared to propranolol and phenylalanine, appear to be consistent with their less than complete absorption in humans.     

盐酸雷尼替丁片在健康志愿者的人体药代动力学和生物等效性

目的:研究国产盐酸雷尼替丁片和葛兰素威康生产的雷尼替丁片(商品名:善卫得)在健康人体内的药代动力学过程,并评价这两种制剂的生物等效性。方法:20例健康男性受试者随机分组、自身对照单次po盐酸雷尼替丁片300 mg后,用反相HPLC法测定血浆中雷尼替丁的浓度,依据血药浓度一时间数据进行有关参数计算及生物等效性评价。结果:对照制剂与试验制剂主要药代动力学参数C_(max)分别为1278.3±449.5 μg·L~(-1)及1200.5±433.1 μg·L~(-1);t_(max)分别为2.73±0.80 h及2.95±0.83 h;t_(1/2)分别为2.97±0.43 h及2.98±0.49 h;AUC_(0→t)分别为5582.2±1428.7 μg·h·L~(-1)及5199.0±1275.0μg·h·L~(-1); AUC_(0→∞)分别为5928.2±1389.3μg·h·L~(-1)及5413.3±1318.0 μg·h·L~(-1);试验制剂相对于对照制剂的生物利用度F为(94.6±16.1)％。结论:试验制剂与对照制剂生物等效。     

石榴健胃胶囊中非法添加尼扎替丁、西咪替丁、法莫替丁、盐酸雷尼替丁和拉呋替丁的检测

目的:建立石榴健胃胶囊中非法添加尼扎替丁、西咪替丁、法莫替丁、盐酸雷尼替丁和拉呋替丁的分析方法.方法:采用高效液相色谱法,以十八烷基硅烷键合硅胶为填充剂的C18柱(4.6 mm×250 mm,5 μm),以甲醇(A)-水(每1 000 mL含磷酸0.3 mL和己烷磺酸钠0.94g)(B)梯度洗脱[0～25 min,A:23％,B:77％;25～ 40 min,A:23％→90％,B:77％→10％;40 ～ 50min,A:23％,B:77％];流量为1.0 mL·min -1;柱温小于30 ℃;检测波长为220 nm.结果:尼扎替丁、西咪替丁、法莫替丁、盐酸雷尼替丁和拉呋替丁的线性范围分别为0.020 34 ～2.542 μg(r ＝0.999 9)、0.020 78～2 598 μg(r＝0.999 9)、0.018 86～2.357 μg(r＝0.999 9)、0.019 66～2.457 μg(r＝1)和0.022 06 ～ 2.757 μg(r ＝0.999 9);回收率(n＝6)分别为101.53％、94.09％、92.24％、93.44％和96.38％;RSD分别为0.81％、0.53％、0.49％、0.90％和0.92％.结论:该方法选择性强,灵敏度高,重复性好,亦可作为石榴健胃胶囊预防非法添加尼扎替丁、西咪替丁、法莫替丁、盐酸雷尼替丁和拉呋替丁的有效分析方法.     

人体内奥美拉唑立体选择性药代动力学研究

研究了８名中国健康男性受试者单剂量口服奥美拉唑（ｏｍｅｐｒａｚｏｌｅ,ＯＰＺ）胶囊２０ｍｇ后（－） ＯＰＺ和（＋） ＯＰＺ在体内药代动力学的立体选择性规律．用手性固定相ＨＰＬＣ法,测定了服药后０５,１．０,１．５,２．０,３．０,４．０,６．０ｈ不同时刻血浆中（－） 和（＋） 对映异构体的浓度刻,绘了相应的浓度 时间曲线,并求出主要药代动力学参数．结果表明,不同时刻血浆中（－） ＯＰＺ的浓度始终高于（＋） ＯＰＺ．ＯＰＺ对映异构体的ＡＵＣ及Ｃｍａｘ比值（－）／（＋）分别为（１．５８９±０．２０１）和（１．４５８±０．２２８）,其药代动力学具有明显的立体选择性（Ｐ＜０．０５）．     

奥美拉唑与西咪替丁预防应激性溃疡出血的Meta分析

摘 要 目的： 对奥美拉唑与西咪替丁预防应激性溃疡出血的临床效果进行评价,为临床应用提供循证医学证据。方法: 以“奥美拉唑”、“西咪替丁”、“应激性溃疡”等为主题词或关键词检索PubMed、Medline、CNKI、万方及维普数据库。两名研究员独立提取资料,并对其方法学质量进行评价。对符合纳入标准的研究采用RevMan5.2软件进行Meta分析。结果: 共纳入17个随机对照试验（奥美拉唑组患者892例,西咪替丁组患者888例）。Meta分析结果显示,在应激性溃疡出血发生率方面,奥美拉唑组与西咪替丁组的差异有统计学意义（OR=0.23,95%CI：0.17～0.32,P<0.000 01）。结论:现有文献分析结果表明,在预防应激性溃疡出血方面,奥美拉唑较西咪替丁可能具有更好的疗效。     

盐酸雷尼替丁胶囊人体药动学和生物等效性研究

目的:评价国产盐酸雷尼替丁胶囊与进口盐酸雷尼替丁片的人体生物等效性。方法:采用反相高效液相色谱法,测定20名健康志愿者随机分组、自身对照单次口服盐酸雷尼替丁胶囊或盐酸雷尼替丁片300mg后不同时刻的血药浓度,计算药动学参数,并进行方差分析和双单侧t检验。结果:盐酸雷尼替丁片与盐酸雷尼替丁胶囊的Cmax分别为(1247.1±547.5)、(1294.8±613.2)μg/L;tmax分别为(2.98±0.73)、(2.73±0.80)h;t1/2分别为(3.17±0.36)、(3.33±0.42)h;AUC0～t分别为(5805.9±1403.5)、(5941.2±1526.3)(μg·h)/L;AUC0～∞分别为(6163.8±1456.4)、(6351.8±1652.7)(μg·h)/L;盐酸雷尼替丁胶囊相对于盐酸雷尼替丁片的生物利用度为(104.3±24.3)%。结论:2种制剂具有生物等效性。     

法莫替丁、雷尼替丁及奥美拉唑治疗急性脑出血并发应激性上消化道出血成本-效果分析

目的:评价法莫替丁、雷尼替丁及奥美拉唑治疗急性脑出血并发应激性上消化道出血的疗效和经济学效果。方法:将180例脑出血并发应激性上消化道出血的患者按给药方案分成法莫替丁组、雷尼替丁组、奥美拉唑组,分别给予法莫替丁、雷尼替丁、奥美拉唑治疗5d,观察疗效,并进行药物经济学分析。结果:法莫替丁组、雷尼替丁组、奥美拉唑组治疗上消化道出血的总有效率分别为87.3%、76.7%、93.8%,成本分别为58、18、430元,成本-效果比分别为66.44、23.47、458.42;相对于雷尼替丁组,法莫替丁组、奥美拉唑组的增量成本-效果比分别为377.36、2409.36。结论:法莫替丁治疗急性脑出血并发应激性上消化道出血最为经济、有效。     

潘生丁、西咪替丁治疗水痘疗效观察

我科于 1997年 3月～ 1999年 12月用潘生丁、西咪替丁治疗水痘 6 0例 ,收到满意疗效 ,现报告如下。1　临床资料1.1　病例选择　全部病例为 3～ 10岁确诊为水痘的患儿 ,表现为典型的皮疹 :斑丘疹、疱疹、结痂同时出现 ,呈向心性分布。随机分为治疗组 6 0例 ,男 35例 ,女 2 5例 ,其中发热 5 6例 ;对照组 5 8例 ,男 32例 ,女 2 6例 ,其中发热 5 3例。两组在年龄、性别、治疗前病情等方面无显著差异。1.2　治疗方法　全部病例均用 10 %炉甘石外涂及抗过敏对症治疗。治疗组在一般治疗基础上加用潘生丁 3～ 5 mg/Kg· d与西咪替丁 15～ 2 0 mg/Kg…     

奥美拉唑与雷尼替丁治疗消化性溃疡临床对比观察

目的：观察两种不同的方案治疗消化性溃疡的临床疗效,探讨治疗消化性溃疡的有效方法。方法：对照组幽门螺杆菌（HP）阳性者给予1周的HP根除治疗,之后给予奥美拉唑肠溶片,连续4周,HP阴性者直接给予奥美拉唑肠溶片20 mg,q d,连续5周。治疗组HP阳性者给予对照组相同的HP根除治疗方案,1周后给予雷尼替丁,连续用药4周,HP阴性者直接给予雷尼替丁,连续用药5周。所有患者在治疗后1周复诊1次,记录腹痛、反酸、上腹烧灼感消化道症状改善情况,并于5周疗程结束时复查胃镜情况。结果：治疗组临床治愈率达到83.33%,明显优越于对照组的57.69%（P〈0.05）,总有效率方面治疗组全部有效,明显优越于对照组的76.92%（P〈0.05）。胃镜下治疗组临床痊愈、总有效率分别为76.67%、96.67%,与对照组的50%、69.23%相比均有明显差异（P〈0.05）。结论：质子泵抑酸剂奥美拉唑在消化性溃疡优越于H2受体拮抗剂雷尼替丁的治疗作用,是临床上值得推广的治疗消化性溃疡的首选药物。     

Influence of (+)-Catechin and Dithiocarb on the Pharmacokinetics of Phenprocoumon, Tolbutamide and Three Inhalation Anesthetics in rats

Pretreatment with (+)-catechin ((+)-cyanidanol-3, Catergen) (200 mg/kg p.o.) did not alter the elimination of intravenously injected phenprocoumon (0.6 mg/kg) or tolbutamide (100 mg/kg) in rats, while dithiocarb (Sodium diethyl-dithiocarbamate) (200 mg/kg p.o.) prolonged only the elimination half-life of phenprocoumon to a small extent. The metabolism of halothane (100 ppm), enflurane (100 ppm) or methoxyflurane (300 ppm) was studied by measuring the disappearance of the compounds from the atmosphere of a closed exposure system. Pretreatment with (+)-catechin did not impair the metabolic removal of all three anesthetics; in the case of enflurane (+)-catechin caused a small, but significant shortening of the elimination half-life, for enflurane and methoxyflurane the uptake of the compounds into the rats seemed to be impaired under the influence of (+)-catechin. Dithiocarb strongly impaired the in vivo metabolism of halothane and methoxyflurane, whereas that of enflurane remained unaffected.     

Meta-Analyses of Cisapride, Omeprazole and Ranitidine in the Treatment of GORD: Implications for Treating Patient Subgroups

OBJECTIVE: Meta-analyses of efficacy results reported in trials of the pharmacological treatment of gastro-oesophageal reflux disease (GORD) with cisapride, omeprazole or ranitidine were performed using randomised, double-blind studies identified by a Medline search covering the years 1984 to 1995. RESULTS: The overall order of efficacy following 12 weeks of acute treatment was omeprazole 40 mg/day (95% cured) > ranitidine 600 mg/day (81% cured) > cisapride 40 mg/day or ranitidine 300 mg/day (approximately 60% cured). However, important differences emerged regarding efficacy in mild versus severe GORD, and in the frequency of relapse. In mild GORD, the cure rate with cisapride 40 mg/day was greater than the cure rate with ranitidine 300 mg/day (56 vs 38%, respectively), and the cure rate with cisapride 80 mg/day was similar to the cure rate with omeprazole 20 mg/day (82 vs 75%, respectively). In severe GORD, the cure rate with cisapride 80 mg/day was half that of omeprazole 20 mg/day (43 vs 87%, respectively) and comparable with that of ranitidine 300 mg/day (50%). Among patients treated acutely with omeprazole, 6-month relapse rates were 17% with omeprazole 20 mg/day maintenance therapy, but 76 to 80% without maintenance therapy. Among patients treated acutely with cisapride, 6-month relapse rates were 33% with 20 mg/day maintenance therapy and only 40% without maintenance therapy, which compare favourably with those following 6 months' maintenance therapy with ranitidine 300 mg/day (49%). CONCLUSION: These results indicate that omeprazole is clearly the treatment of choice for severe GORD, suggest that cisapride may be the treatment of choice for mild GORD, and indicate that either of these two treatments is superior to ranitidine for the prevention of relapse. Further comparative clinical studies are needed, designed specifically to delineate the most appropriate drug therapy for various subgroups of GORD patients.