西咪替丁联合阿昔洛韦治疗小儿水痘的临床分析

目的 探讨西咪替丁联合阿昔洛韦治疗小儿水痘的临床疗效。方法 选取80例水痘患儿,随机数字表法分为两组,对照组患儿（40例）静脉滴注阿昔洛韦注射液15 mg/（kg·d）,观察组患儿（40例）静脉滴注西咪替丁注射液和阿昔洛韦注射液各15 mg/（kg·d）,两组均治疗7 d。观察并记录两组患儿临床疗效,治疗后患儿退热时间、皮疹结痂时间、瘙痒消失时间,治疗前后HAMA评分及治疗期间不良反应情况,评价西咪替丁联合阿昔洛韦治疗小儿水痘的临床疗效。结果 观察组治疗有效率87.5%,对照组治疗有效率65.0%,观察组治疗有效率高于对照组,差异有统计学意义（P<0.05）。治疗后观察组患儿退热时间、皮疹结痂时间、瘙痒消失时间均短于对照组,差异有统计学意义（P<0.05）。治疗前,两组患儿HAMA评分相比,无统计学差异;治疗后,两组患儿HAMA评分均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显低于对照组,差异有统计学意义（P<0.05）。治疗期间,两组不良反应率无明显差异。结论 西咪替丁联合阿昔洛韦治疗小儿水痘效果良好,能较快改善水痘临床症状,减轻小儿焦虑情绪,治疗方案安全性高,值得临床推广使用。     

Effect of intragastric pH on control of peptic ulcer bleeding

BACKGROUND: We have performed series studies to investigate the effect of intragastric pH on control of peptic ulcer bleeding. In laboratory and animal studies, both platelet aggregation and gastric mucosal bleeding time were shown to be extremely sensitive to different pH levels. Platelet aggregation decreased significantly at pH > or = 6.8 and gastric mucosal bleeding time fell significantly at pH > or = 6.4. In a prospective clinical trial, primed infusions of different dosages of omeprazole (8 or 4 mg/h) after a bolus (40 mg) produced consistently high intragastric pH values in patients with bleeding duodenal ulcer. These results were not significantly different from that obtained from omeprazole 40 mg bolus treatment every 12 h (P > 0.05). However, primed injection with cimetidine (800 mg/12 h) was less effective (P < 0.05). METHODS: In a retrospective analysis, 303 patients with bleeding peptic ulcer who were treated with cimetidine and 326 patients who were treated with omeprazole were compared. RESULTS: The emergency surgery (4.91%) and mortality rates (1.84%) in the omeprazole group were not significantly different (P > 0.05) from those (7.28 and 1.99%) in the cimetidine group. However, the standardized emergency surgery rate of the omeprazole group (3.28%) was significantly lower than that (9.28%) of the cimetidine group (P < 0.05). CONCLUSION: We conclude that increased intragastric pH to at least 6.4 with omeprazole is helpful in controlling peptic ulcer bleeding. Chinese patients require a lower dose of omeprazole than their Western counterparts to control ulcer bleeding.     

替代对照品法用于石杉碱甲片含量测定的研究

 目的建立HPLC替代对照品测定石杉碱甲片含量的测定方法。方法在不同的条件下测定替代对照品西咪替丁对石杉碱甲对照品的校正因子,利用校正因子和替代对照品西咪替丁进行石杉碱甲片的含量测定。结果石杉碱甲和西咪替丁分别在2.5～160mg·L^-1(r=1.0000)和0.1～20.0mg·L^-1(r=1.0000)内与峰面积呈良好的线性关系(n=7),测得校正因子f=2.3624,用替代对照品测定方法测得回收率为97.0%(n=5),RSD=1.7%。结论本实验首次在高效液相色谱仪上使用替代对照品测定了石杉碱甲片含量,结果证明,用替代对照品进行药品质量控制是可行的、实用的。     

围手术期应用西米替丁对结直肠癌TIL浸润及HLA-DR表达的影响

目的研究表明西米替丁(CIM)能增强胃肠癌患者机体的免疫力,本实验探讨了CIM对结直肠癌(CRC)肿瘤浸润淋巴细胞(TIL) 及肿瘤间质细胞HLA-DR表达的影响,以了解CIM在CRC局部免疫中的作用。方法将49例CRC随机分为治疗组与对照组,治疗组25例术前1周开始口服CIM；对照组进行常规治疗,不服用CIM；手术前后比较肿瘤间质TIL浸润程度及HLA-DR表达的变化。结果 CIM治疗组手术前后TIL的明显反应,由治疗前的32％(8／25)上升到治疗后的76％(19／25),差别有显著性(P＜0.005)；而对照组仅由治疗前的25％(6／24)上升至33％(8／24),无显著统计学差异。治疗组HLA-DR的高表达由治疗前的36％(9／25)上升到治疗后的72％(18／25),有显著差异性,而对照组由41.7％(10／24)上升至45.8％(11／24),无显著差异(P＞0.50)。结论术前应用CIM能增加CRC患者肿瘤组织TIL的浸润及增强间质细胞HLA-DR的表达,表明CIM能增加CRC患者的局部抗肿瘤免疫力。     

口服西米替丁对肌酐清除率的影响和意义

为探讨使用西米替丁对肾病患儿肌酐清除率 (Ccr)的影响 ,将53例肾小球疾病患儿分为两组 :A组28例Ccr≥80ml/(min·1.73m2)和B组25例Ccr<80ml/(min·1.73m2)。观察对象实验当天分别留7a.m.～9a.m.和10a.m.～12a.m.尿,测2小时尿肌酐 ;9am抽血测血肌酐 ,并口服西米替丁0.8g/1.73m2。分别计算服药前、后2小时肌酐清除率 (Ccr1、Ccr2)并行统计分析。结果发现两组患儿Ccr2均较Ccr1显著降低 (P<0.05) ,但A组患儿 (Ccr1 -Ccr2)的均数与同组Ccr2均数的比值仅为3.9% ;B组患儿 (Ccr1 -Ccr2)的均数与同组Ccr2均数的比值则为103.4 %。对数回归示 ,(Ccr1 -Ccr2)/Ccr2与Ccr2呈显著负相关 ,(r= -0.791 ,P<0.05)。提示对肾功能不全患儿可用服西米替丁后的Ccr评价其肾功能。     

西咪替丁缓释片溶出度测定的研究

 采用紫外分光光度法分别对西咪替丁普通片剂及缓释片的溶出度进行了测定和比较。缓释片溶出Ｔ＿（５０）为１．３２～２，１０ｈ，而普通片在１５ｍｉｎ内全部溶解，缓释片能明显延长溶出半衰期。未测定方法快速、简便，适宜生产中控制药品质量，从而进一步指导生产。     

Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide

AIMS: The aim of this open-label, placebo-controlled, randomized, four-period crossover study was to determine the effects of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of a single dose of dofetilide. METHODS: Twenty healthy male subjects received 100 or 400 mg twice daily of cimetidine, 150 mg twice daily of ranitidine, or placebo for 4 days. On the second day, a single oral 500 microg dose of dofetilide was administered immediately after the morning doses of cimetidine, ranitidine, or placebo. Treatment periods were separated by 1-2 weeks. Pharmacokinetic parameters were determined from plasma and urinary dofetilide concentrations; prolongation of the QTc interval was determined from three-lead electrocardiograms. RESULTS: Ranitidine did not significantly affect the pharmacokinetics or pharmacodynamics of dofetilide; however, a dose-dependent increase in exposure to dofetilide was observed with cimetidine. When dofetilide was administered with 100 and 400 mg of cimetidine, the area under the plasma concentration-time curve of dofetilide increased by 11% and 48% and the maximum plasma dofetilide concentration increased by 11% and 29%, respectively. The respective cimetidine doses reduced renal clearance of dofetilide by 13% and 33% and nonrenal clearance by 5% and 21%. Dofetilide-induced prolongation of the QTc interval was enhanced by cimetidine; the mean maximum change in QTc interval from baseline was increased by 22% and 33% with 100 and 400 mg of cimetidine, respectively. However, the relationship between the prolongation of the QTc interval and plasma dofetilide concentrations was unaffected by cimetidine or ranitidine; a 1 ng ml-1 increase in plasma dofetilide concentration produced a 17-19 ms prolongation of the QTc interval. Dofetilide was well tolerated, with no treatment-related adverse events or laboratory abnormalities. CONCLUSIONS: These results suggest that cimetidine increased dofetilide exposure by inhibiting renal tubular dofetilide secretion, whereas ranitidine did not. This effect is not an H2-receptor antagonist class effect but is specific to cimetidine. If therapy with an H2-receptor antagonist is required, it is recommended that cimetidine at all doses be avoided; since ranitidine has no effect on dofetilide pharmacokinetics or prolongation of the QTc interval, it can be seen as a suitable alternative.     

Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine

AIMS: To evaluate whether ketoconazole or cimetidine alter the pharmacokinetics of loratadine, or its major metabolite, desloratadine (DCL), or alter the effects of loratadine or DCL on electrocardiographic repolarization in healthy adult volunteers. METHODS: Two randomized, evaluator-blind, multiple-dose, three-way crossover drug interaction studies were performed. In each study, subjects received three 10 day treatments in random sequence, separated by a 14 day washout period. The treatments were loratadine alone, cimetidine or ketoconazole alone, or loratadine plus cimetidine or ketoconazole. The primary study endpoint was the difference in mean QTc intervals from baseline to day 10. In addition, plasma concentrations of loratadine, DCL, and ketoconazole or cimetidine were obtained on day 10. RESULTS: Concomitant administration of loratadine and ketoconazole significantly increased the loratadine plasma concentrations (307%; 90% CI 205-428%) and DCL concentrations (73%; 62-85%) compared with administration of loratadine alone. Concomitant administration of loratadine and cimetidine significantly increased the loratadine plasma concentrations (103% increase; 70-142%) but not DCL concentrations (6% increase; 1-11%) compared with administration of loratadine alone. Cimetidine or ketoconazole plasma concentrations were unaffected by coadministration with loratadine. Despite increased concentrations of loratadine and DCL, there were no statistically significant differences for the primary electrocardiographic repolarization parameter (QTc) among any of the treatment groups. No other clinically relevant changes in the safety profile of loratadine were observed as assessed by electrocardiographic parameters (mean (90% CI) QTc changes: loratadine vs loratadine + ketoconazole = 3.6 ms (-2.2, 9.4); loratadine vs loratadine + cimetidine = 3.2 ms (-1.6, 7.9)), clinical laboratory tests, vital signs, and adverse events. CONCLUSIONS: Loratadine 10 mg daily was devoid of any effects on electrocardiographic parameters when coadministered for 10 days with therapeutic doses of ketoconazole or cimetidine in healthy volunteers. It is concluded that, although there was a significant pharmacokinetic drug interaction between ketoconazole or cimetidine and loratadine, this effect was not accompanied by a change in the QTc interval in healthy adult volunteers.     

Lack of effect of omeprazole,cimetidine, and ranitidine on the pharmacokinetics of ethanol in fasting male volunteers

Summary The effects of three gastric antisecretory drugs on the pharmacokinetics of ethanol have been studied in a randomized crossover experiment.Male medical students (n=12) took ethanol 0.8 g/kg body weight at 08.00 h after an overnight fast. On seven successive days before drinking ethanol they were given omeprazole 20 mg, cimetidine 800 mg, ranitidine 300 mg, or no drug, with a period of at least 7 days between treatments.The peak blood ethanol concentration of 21.9 to 22.8 mmol·l^–1 occurred at 64 to 70 min after the end of drinking.The rate of disappearance of ethanol from the blood ranged from 3.0 to 3.3 mmol·l^–1·h^–1 and the rate of removal from the whole body ranged from 8.0 to 8.5 g·h^–1.The apparent volume of distribution of ethanol was almost the same for all four treatments: mean 0.68 l·kg^–1, corresponding to a mean total body water of 441 (59% body weight). Mean areas under the concentration-time profiles of ethanol ranged from 83 to 87 mmol·l^–1·h for the four treatments.It is concluded that omeprazole, cimetidine and ranitidine do not alter the kinetics of a moderate dose of ethanol.     

The Effect of Cimetidine on Verruca Plana Juvenilis: Clinical Trials in Six Patients

Cimetidine is an H₂-receptor antagonist which is mainly used to treat gastrointestinal diseases. Recently, many authors have suggested that cimetidine has the ability to reverse acquired tolerance to dinitrochlorobenzene (DNCB). We have used cimetidine in six patients with verruca plana who showed no therapeutic response to DNCB. Four of them responded and showed complete disappearance of the verruca plana. The mean duration of oral cimetidine administration (1.2 g/day) was 4 weeks until the disappearance. Therefore, we suggest that oral cimetidine can be used as an effective and safe adjunctive modality for the treatment of verruca plana.