摘要:

SUMMARYSulphasalazine is composed of sulphapyridine and mesalazine (5‐aminosalicylic acid, 5‐ASA or mesalazine) joined by an azo bond. Sulphasalazine has been used clinically for 40 years but less than 10 years ago it was recognized that the active moiety is 5‐ASA. Sulphapyridine appears to act only as a carrier molecule to deliver mesalazine to the bowel, yet it is the sulphapyridine which appears to be responsible for many of the adverse effects observed with sulphasalazine. Normally, mesalazine is rapidly absorbed from the upper gastrointestinal tract. Since the action of mesalazine is thought to be locally at the site of disease in the intestine, the 5‐ASA must be ‘protected’ to ensure its release in the terminal ileum and colon, the site of bowel inflammation in patients with Crohn's disease or ulcerative colitis. Recent clinical studies have confirmed the efficacy of topical (suppositories and enemas) therapy for ulcerative proctitis and left‐sided colitis; oral mesalazine has been proven to be useful for the treatment of acute ulcerative colitis and for the maintenance of remission. There is preliminary evidence for the clinical usefulness of mesalazine in acute Crohn's disease as well as for the maintenance

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00515.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYHydroxyproline concentration in oesophageal mucosal biopsies was used as an index of collagen in an attempt to evaluate the potential for stricture formation in patients with progressive systemic sclerosis. Eight patients suffering from progressive systemic sclerosis with complicating gastro‐oesophageal reflux, 8 patients with idiopathic gastro‐oesophageal reflux, and 7 normal controls were compared. Acid gastro‐oesophageal reflux was assessed with 24‐h pH‐metry; degree of oesophagitis was evaluated both endoscopically and histopathologically. The patients with progressive systemic sclerosis were investigated at the start of the study and later when healing of oesophagitis was accomplished with omeprazole therapy. The hydroxyproline concentration was significantly increased (P<0.01) in the oesophageal mucosa from patients with progressive systemic sclerosis (median 21.8 nmol/mg) as compared to patients with idiopathic gastro‐oesophageal reflux (median 6.4 nmol/mg) and normal controls (median 8.1 nmol/mg).Hydroxyproline concentration in oesophageal mucosa from patients with progressive systemic sclerosis decreased significantly and to a normal level (median 6.5 nmol/pg;P= 0.014) when healing of oesophagitis w

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00516.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYGR122311X (ranitidine bismuth citrate Glaxo Group Research Ltd) is a bismuth compound with histamine H2‐receptor antagonist activity. The gastric acid antisecretory activity of three oral dosage regimens of GR122311X was compared with placebo and 150 mg ranitidine b.d. The median 24‐h integrated intragastric acidity was 38, 26 and 18% of the median placebo value during dosing with GR122311X 196, 391 and 782 mg b.d., respectively. The 24‐h acid suppression with GR122311X 391 mg b.d. was not significantly different to that produced by 150 mg ranitidine b.d. (24% of placebo acidity). The median 24‐h urinary bismuth excretion increased with rising dosage of GR122311X from 19.2 μg with 196 mg b.d., to 36.4 μg with 391 mg b.d., to 68.7 μg with 782 mg b.d. In conclusion, GR122311X is an effective antisecretory agent with modest systemic bismuth

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00517.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYWe have investigated the absorption and urinary excretion of tripotassium dicitrato bismuthate during a treatment course of 4 weeks in 7 patients with normal renal function (creatinine clearance 115 ± 29 ml/min; mean ± S. D.), in 7 patients with impaired renal function (creatinine clearance = 34 ± 19 ml/min) and in 4 dialysed patients. Following the first dose of tripotassium dicitrato bismuthate (216 mg bismuth b.d.), and after 2 and 4 weeks of treatment (dialysed patients received only 108 mg/b.d.), plasma and urine concentrations of bismuth were monitored for 2 and 24 h, respectively. After stopping therapy plasma and urine concentrations of bismuth were followed for 4 and 6 weeks, respectively. In all three groups of patients small amounts of bismuth (mean values 0.26 to 0.28% of dose) were rapidly (transient mean peak concentrations between 40 and 134 μg/L) reached within about 30 to 40 min, absorbed and alasma levels demonstrated a wide intra‐ and inter‐individual variability. Absorption profiles were not altered during the treatment course; however, the trough plasma concentration of bismuth demonstrated an about 3‐ to 5‐fold accumulation (correlated to creatinine clearance) from about 5 μg/L to 15 μ/L (normal renal function) or to 20–25 μ/L (impaired renal function). Pre‐study bismuth levels could be detected within 2 to 4 weeks after stopping therapy in all subjects whereas urinary concentrations were still elevated 6 weeks after the course of treatment.Our results indicate that tripotassium dicitrato bismuthate is absorbed in very low amounts during standard therapy. However, dependent on renal function, accumulation to non‐toxic levels does occur during a course of treatment. It appears prudent to halve tripotassium dicitrato bismuthate dosage in patients with severe renal insufficiency (creatinine clearance ± 20 ml/min) to avoid any possible toxic risks. In such patients monitoring of the plasma bismuth concentration might be helpful, especially if longer or repeated tre

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00518.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe effect of cisapride on duration of post‐operative ileus after surgery was investigated in a randomized, double‐blind, placebo‐controlled study. Patients undergoing elective upper gastrointestinal (n= 47) or colonic (n= 22) surgery were pre‐operatively randomly allocated to treatment with either cisapride 30 mg t.d.s., by rectal administration, or placebo. Treatment started exactly 48 h after surgery if the patient at this time had not passed stool. Time to passage of first stool after surgery was estimated.Mean time to passage of stool was 85 (32) h (s.d.) for cisapridetreated and91 (43)h for placebo‐treated patients. No difference between the treatment groups was noted.Treatment with cisapride did not shorten the duration of postoperative ileus after either upper gastrointestinal or coloni

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00519.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThirty‐seven patients suffering an attack of acute distal ulcerative colitis of mild or moderate severity were randomized in a double‐blind, doubledummy fashion to receive either 800 mg oral mesalazine four times daily (18 patients) or steroid enemas twice daily (19 patients) for 4 weeks. Both treatments were well tolerated with no adverse effects. Three patients in each group were withdrawn because of clinical deterioration but both treatments produced significant clinical improvement with decreases in stool frequency and scores for urgency, bleeding and tenesmus. There were no significant differences between the treatments although there was a slight trend in favour of the enemas for reduction in rectal bleeding. Activity of the colitis as graded at sigmoidoscopy also decreased significantly with both treatments and there were corresponding improvements in histological parameters of inflammatory activity assessed with the aid of a computerized morphometric system. Little correlation was seen between clinical, sigmoidoscopic and histological chan

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00520.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYOmeprazole has been shown in previous studies to inhibit the hepatic metabolism of selected drugs. Quinidine is an antiarrhythmic and antimalarial agent with a low therapeutic index. We therefore examined the effect of 40 mg omeprazole daily for one week or placebo on the pharmacokinetics and pharmacodynamics of a single 400 mg dose of quinidine in 8 healthy volunteers in a double‐blind crossover study.During placebo and omeprazole treatment, there was no significant difference in area under the time–plasma quinidine concentration curve, (17.0 ± 4.83 μg.h/ml, 18.6 ± 4.43 μg.h/ml, respectively;P>0.2) or renal clearance of quinidine (56.2 ± 26.0 ml/min, 55.6 ± 12.7 ml/min, respectively;P>0.5). Quinidine unbound fraction in plasma (0.170 ± 0.041vs.0.166 ± 0.041 in the presence of omeprazole;P>0.5) was not altered by omeprazole. Peak plasma quinidine concentration and the time this occurred did not differ. Omeprazole also had no effect on these parameters for the metabolite 3‐hydroxyquinidine. There was no significant difference in the change in the corrected Q—T interval on the electrocardiogram due to quinidine (mean area under the time versus ±Q–Tccurve = 351 ± 192 ms. h, placebo; 414 ± 303 ms. h, omeprazole) showing that quinidine pharmacodynamics were unaltered by omeprazole. We conclude that omeprazole does not affect the pharmacok

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00521.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYProstaglandin analogues, used in the treatment of duodenal and benign gastric ulcer and in the prevention of gastric ulceration caused by nonsteroidal anti‐inflammatory drugs, are frequently associated with gastrointestinal side effects, particularly diarrhoea and abdominal cramps. We investigated the effects of misoprostol, a prostaglandin E1derivative, on bowel motility and faecal loss of fat, water and bile acids in relation to its postprandialvs. preprandial administration. Twelve healthy subjects participated in a double‐blind crossover study comparing three 5‐day courses of therapy with a washout period of 1‐2 weeks between courses. Following a Latin Square design, the dosing regimens were (a) 400 μ misoprostol b.d. after meals and placebo b.d. before meals; (b) 400 μ misoprostol b.d. before meals and placebo b.d. after meals; (c) placebo before and after meals. Orocaecal transit time measured by H2breath tests following lactulose administration, was shortest during pre‐prandial dosing but was also significantly decreased during post‐prandial dosing. The overall treatment difference was highly significant (P<0.001), and the difference between each pair of treatments was also statistically significant. Whole bowel transit time studied by means of3H‐PEG 4000 determination in stools, was shorter for the two misoprostol regimens but statistical significance was borderline. The number of stools passed per day was similar in the three groups. During both misoprostol dosing periods, stools were less formed and their content of water, fat and bile acids was higher. There was also more urgency, flatulence, abdominal pain and nausea. It is concluded that the gastrointestinal side effects caused by misoprostol are mainly based on an increased orocaecal transit time. The effects are more important when the drug is administered before meals t

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00522.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYFiftyHelicobacter pylori‐ (H. pylori)positive patients entered an open study and were assigned to one of four treatment regimens comprising: pivampicillin (500 mg b.d.) for 2 weeks tripotassium dicitrato bismuthate (tablet or liquid form) for one month.The14C‐urea breath test was used to evaluate clearance (negative at the end of treatment) and eradication (negative at 1 month posttreatment) ofH. pylori. Clearance rates were 20% (2/10) after pivampicillin alone, 86% (12/14) after tripotassium dicitrato bismuthate tablets (240 mg b.d.) plus pivampicillin, 67% (6/9) after tripotassium dicitrato bismuthate tablets (120 mg q.d.s.) plus pivampicillin, and 100% (13/13) after tripotassium dicitrato bismuthate liquid (120 mg in 5 ml q.d.s.) plus pivampicillin. The eradication rates were 0% (0/10), 13% (2/15), 0% (0/11) and 54% (7/13), respectively.Combination of the results from the 2 tripotassium dicitrato bismuthate tablet/pivampicillin groups gave an eradication rate of 7.7% (2/26) which was significantly lower than the 53.9% (7/13) obtained with tripotassium dicitrato bismuthate liquid/pivampicillin (P<0.02).In conclusion, a liquid tripotassium dicitrato bismuthate pivampicillin combination may be of special use in the treatment ofH. pylori‐positive patients when triple therapy is contraindicated (e.g. patient sensitivity/allergy to metronidazole) or when theH. pyloriisolate is resistant to metronid

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00523.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYTen dyspeptic patients were treated with 1 g sucralfate q.d.s. for six weeks. The plasma aluminium concentration and 24‐h urinary aluminium excretion were measured at 3‐weekly intervals before, during and after treatment with sucralfate. Compared with before treatment, there were significant rises in the median plasma aluminium concentration at 3 and 6 weeks during treatment with sucralfate (6 μ/L to 13 and 12 μ/L). The median 24‐h urinary aluminium excretion rose significantly from a pretreatment level of 20 μ to 71 and 78 μ after 3 and 6 weeks of treatment; the significant increase of urinary aluminium excretion persisted for three weeks after cessation of treatment (52 μ/24 hours), but thereafter urinary excretion was not significantly different from pretreatment. The results are consistent with significant absorption and tissue accumulation of aluminium during standard treatment with sucralfate in individuals with normal rena

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00524.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY