摘要:

SUMMARYSerotonin (5‐hydroxytryptamine; 5‐HT) is found in the enteric nervous system where it has been implicated in controlling gastrointestinal motor function. A number of receptor or recognition sites have been identified in the gut, but recently most attention has focused on the 5‐HT3and 5‐HT4receptors. The functional role of the 5‐HT3receptor remains incompletely understood, but it is probably involved in the modulation of colonic motility and visceral pain in the gut. A number of selective 5‐HT3antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride. While the substituted benzamide prokinetics (for example, metoclopramide, cisapride) also block 5‐HT3receptors in high concentrations, their prokinetic action is believed to be on the basis of their agonist effects on the putative 5‐HT4receptor. Some 5‐HT3antagonists have 5‐HT4agonist activity (for example, renzapride, zacopride) and others do not (for example, ondansetron, granisetron), while tropisetron in high concentrations is a 5‐HT3antagonist. Based on the pharmacological data, it has been suggested that specific 5‐HT antagonists and agonists may prove to be beneficial in a number of gastrointestinal disorders including the irritable bowel syndrome, functional dyspepsia, non‐cardiac chest pain, gastrooesophageal reflux and refractory nausea. In this review, the rationale for the use of these compounds is discussed, and the available experiment

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00050.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe discovery ofHelicobacter pylorihas stimulated great interest in its role in gastritis, non‐ulcer dyspepsia and peptic ulceration. Treatment regimens to eradicate this organism from gastric mucosa have also received considerable attention. Current recommendations limit the use of triple drug combinations only to specific patient group

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00051.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYAcetorphan is a potent enkephalinase inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro‐caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total orocaecal times were 303 ± 32 minvs.287 ± 27 min and colonic transit times 25.8 ± 5.8 hvs. 31.3 ± 5.5 h after acetorphan and placebo, respectively (means ± S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulfphasalazine and radiopaque markers methods can be simultaneously applied in the same

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00052.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYIn a 48‐week study of 319 duodenal ulcer patients, symptomatic self‐care with an histamine H2‐receptor antagonist (flexible self‐chosen dosing with cimetidine 0, 400 or 800 mg/day) was compared with maintenance treatment (cimetidine 400 mg nocte). The rate of withdrawal from the study was similar in both groups. The mean consumption of cimetidine 400 mg tablets was significantly higher in the maintenance group (7.2vs. 5.4 tablets/week; P<0.0001), but the mean cumulative number of days with ulcer symptoms was higher in the symptomatic self‐care group (47.2vs.29.1 days in 48 weeks). The estimated number of days of work‐loss due to ulcer symptoms was similar in both groups (approximately 4 days in the 48 weeks of observation).It is concluded that symptomatic self‐care using an H2‐antagonist can provide not only an economic but also an effective strategy for the long‐term management of uncomplicated du

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00053.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYWe have performed a retrospective study of 103 patients with either peptic ulcer or non‐ulcer dyspepsia, infected with metronidazole‐sensitive strains ofHelicobacter pylori(H. pylori), who were treated with a combination of tripotassium dicitrato bismuthate and metronidazole for a period of at least two weeks.Dual therapy with tripotassium dicitrato bismuthate plus metronidazole showed similarly high eradication rates (≥ 80%) ofH. pylorifrom patients irrespective of age, gender or clinical diagnosis. Most importantly, dual therapy achieved a similar eradication rate ofH. pyloriinfection in 41 patients who had previously been treated with tripotassium dicitrato bismuthate alone or in combination with an antibiotic other than metronidazole. It therefore appears thatH. pyloridoes not become resistant to treatment with tripotassium dicitrato bismu

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00054.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe present study examined whether histamine could affect the growth of the enterochromaffin‐like (ECL) cell and the parietal cell. The effects of the unsurmountable histamine H2‐receptor antagonist loxtidine (80 mg/kg) and the H+, K+‐ATPase inhibitor omeprazole (100 μmol/kg) were compared in female Sprague‐Dawley rats. Both drugs were given by gavage once daily for 3 months. Omeprazole induced a more pronounced and sustained hypergastrinaemia than loxtidine. In spite of marked hypergastrinaemia during most of the day, even in the loxtidine‐treated rats, the weights of the stomach and oxyntic mucosa were elevated only in the omeprazole‐treated rats. The ECL cell density was slightly higher in the loxtidine‐ than in the omeprazole‐treated rats. Both treatments elevated the gastrin‐stimulated histamine release from the vascularly perfused stomach. The parietal cell density was unaffected by omeprazole treatment, whereas it tended to be reduced in the loxtidine‐treated rats. Simultaneous administration of loxtidine and omeprazole reduced the sustained hypergastrinaemia induced by omeprazole given alone. The present study may indicate that histamine inhibits the growth of the ECL cell, but further studies are needed to elucidate if histamine has any trophic effect o

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00055.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe hydrocortisone pharmacokinetic profiles of hydrocortisone acetate foam (Proctocort) administered rectally was assessed in healthy volunteers and patients with ulcerative colitis or X‐irradiation colitis. Endogenous production of hydrocortisone was suppressed by dexamethasone. Comparison of these data with those obtained after intravenous administration enabled assessment of absolute bioavailability, which was 30.0 ± 15.1% in healthy volunteersvs.16.4 ± 14.8% in patients (P= 0.09). Maximal concentrations of hydrocortisone were also decreased in patients, 277 ± 215 nmol/Lvs.610 ± 334 mmol/L (P= 0.03). There was a nonsignificant tendency to faster absorption of hydrocortisone in patientsvs.healthy volunteers, as the times to peak concentration were, respectively, 2.5 ± 1.2 hvs.2.8 ± 0.8 h (P= 0.64), and the mean absorption times were 1.96 ± 1.45 h vs. 2.54 ± 1.62 h (P= 0.46). Thus, rectal inflammation resulted in a lower absorption of hydrocortisone. In addition systemic plasma levels remained in the physiological range, so that only minor side effects are to be

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00056.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThis study examined the effects of dose and time of administration of lansoprazole on gastric pH and serum gastrin in healthy male volunteers. Three groups of six subjects received 10, 20 or 60 mg doses of lansoprazole or placebo. Doses were administered at 22.00 hours daily for 7 days. An additional 18 subjects received once daily 30 mg oral doses of lansoprazole or placebo; these subjects were dosed at either 08.00 hours or 22.00 hours in a randomized, crossover fashion with a 2‐week washout period. Gastric pH was monitored for 24 h following the first and final dose, and 1 week following the completion of dosing.Lansoprazole, at all doses except 20 mg/day, significantly increased the median 24‐hour gastric pH following 7 days of dosing (P<0.05). In addition, morning dosing in the 30‐mg crossover group led to a higher 24‐h median pH than evening dosing (P= 0.003). There was no difference in night‐time median pH between morning and evening dosing. Morning dosing also led to a significant increase in gastric pH on study Day 1 (P<0.05). Plasma concentrations of lansoprazole were highly variable between subjects, but there was a significant correlation between AUC and the median 24‐h gastric pH. Plasma concentrations and AUCs were higher on Day 7 than on Day 1 for subjects receiving 10 or 20 mg, but not for those receiving 30 or 60 mg doses. Lansoprazole bioavailability demonstrated a circadian effect manifested by higher plasma concentrations following morning dosing. Serum gastrin concentrations were elevated in all active medica

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00057.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYPantoprazole selectively blocks gastric parietal cell H+,K+‐ATPase. To define a dosage regimen for clinical trials we compared the effect of pantoprazole 40 and 60 mg daily on 24‐h intragastric acidity and plasma gastrin concentrations using a double‐blind, randomized, cross‐over design. Eleven men took each of the three regimens (placebo, 40, 60 mg) for 5 days. On Day 5, 24‐h pHmetry and plasma gastrin profile were performed. A consistent decrease in intragastric acidity with each dosage regimen was shown by a rise in 24‐h median pH from 1.4 (1.2–1.8, IQR) on placebo to 2.3 (1.8–4.4,P= 0.0022) during pantoprazole 40 mg and to 3.5 (2.6–4.9,P= 0.0017) during 60 mg. Pantoprazole 40 and 60 mg maintained the intragastric pH above 3 for 33% and 58% of time, respectively, compared with 15% time with placebo. Twenty‐four‐hour integrated plasma gastrin concentration rose from 478 to 1798 and 1962 pmol.h/L, respectively. The drug was well tolerated. The decrease of acidity was dose related and should result in clinical efficacy similar to other antisecretory drugs. It is not known whether higher doses might abolish acid secretion. The optimal dose of pantoprazole is

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00058.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYH2‐receptor antagonists are conventionally given at night. However, it remains unproven whether this regimen affords superior acid inhibition or healing rates for patients with duodenal ulcers compared to morning dosing. We have therefore examined the acid inhibitory effect of 300 mg ranitidine at night compared to 300 mg ranitidine in the morning in 8 normal male subjects. Intragastric acidity was measured by the radiotelemetry method and acid inhibition calculated from the percentage decrease in the area under the curve for hydrogen ion activity against time. Night‐time ranitidine resulted in a significantly better (P<0.02) decrease of intragastric acidity than the same dose given in the morning (66.8 (61.8–77.6)%vs.34 (15.5–49.1)%). This difference was found to be due to the fact that morning ranitidine inhibited gastric acid secretion when the intragastric acidity was already buffered by food. These data support the superiority of nocturnal dosing with H2‐an

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00059.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY