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  • 1
    Electronic Resource
    Electronic Resource
    Influence of digestive secretions and food on intestinal absorption of nicardipine (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 165-171 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; pharmacokinetics ; gastrointestinal absorption ; influence of food ; intestinal perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of digestive absorption in the pharmacokinetics of nicardipine has been studied by the perfusion technique. Nicardipine (40 mg) was perfused in six healthy subjects at 5 ml/min for 2 h either in isotonic saline with (Experiment A) or without (B) an occlusive balloon isolating the test segment from digestive secretions, or in a nutrient solution (Experiment C). In Experiments A and B, 100% of nicardipine was absorbed from the jejunal lumen in a 25 cm test segment and in Experiment C it was slightly lower (94%). There was no relationship between the absorption of nicardipine and water movement or bile salt concentration in the jejunum. Nicardipine was already present in the first plasma sample taken after 15 min and the peak level was found at the end of the perfusion. The areas under the curves differed widely between subjects, because of interindividual variation in the first pass effect, but they were similar in Experiments A, B and C. The experimental data showed a good fit to a mode involving a two-phase absorption process. The first phase was associated with intestinal perfusion (zero order process) and the second with passage accross the intestinal wall (1st order process). In three further healthy subjects, nicardipine in saline was perfused in the jejunum and then in the ileum on consecutive days. Mean plasma levels over time were similar. The study showed that absorption of nicardipine both from the jejunum and the ileum was complete and was especially rapid. The food-induced change in the kinetics of absorption from the jejunum was too small to affect the pharmacokinetic parameters of nicardipine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614554
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  • 2
    Electronic Resource
    Electronic Resource
    Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 395-399 
    Details
    ISSN: 1432-1041
    Keywords: Prednisone ; Prednisolone metasulfobenzoate ; bioavailability ; intestinal infusion ; absorption ; presystemic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of intestinal absorption in the differential availability of prednisone (PN) and prednisolone metasulfobenzoate (PO-MS), which might account for clinical resistance to PO-MS, has been studied by an infusion technique. In a randomized cross-over design trial, a solution in isotonic saline of PN or PO-MS (115 mg·l−1 was infused at 5 ml·min−1 for 2 h, into a 25 cm segment of jejunum in 8 healthy fasting subjects. The intestinal content was partly collected and the flow rate at the end of the test segment was determined by using a water movement marker (PEG 4000). Plasma, intestinal and urine concentrations of PN and PO were determined by liquid chromatography. From the data on PO, the active molecule, the systemic availability of PO-MS was significantly smaller than of PN, with the respective mean AUCs being 1.71 and 3.60 mg·h−1. The difference was associated with smaller mean Cmax, 0.20 vs 0.64 mg·l−1, higher mean tmax, 2.94 vs 2.06 h and lower mean ka, 0.98 vs 2.18 l/h after PO-MS. No significant difference was found in the half-life or renal clearance of the formulations tested. The mean MRT was significantly increased after PO-MS, 6.82 vs 5.30 h. The observed difference probably reflected a difference in intestinal absorption. The mean absorption in the test segment of PO-MS was significantly smaller at 17.4 vs 85.5% for PN. The ester form may be a limiting factor in the intestinal absorption of PO. Therefore, the choice of PN or PO-MS should follow the therapeutic indication, depending on whether a major systemic effect or a prolonged intestinal local effect is preferred.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316481
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  • 3
    Electronic Resource
    Electronic Resource
    Second-line treatment for failure to eradicate Helicobacter pylori: a randomized trial comparing four treatment strategies (2003)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 18 (2003), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim : To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed.Methods : In this study named StratHegy patients (n = 287) were randomized to receive one of three empirical triple therapy regimens or a strategy based on antibiotic susceptibility. The empirical regimens were omeprazole, 20 mg b.d., plus amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d., for 7 days (OAC7), clarithromycin, 500 mg b.d., for 14 days (OAC14) or metronidazole, 500 mg b.d., for 14 days (OAM14). In the susceptibility-based strategy, patients with clarithromycin-susceptible strains received OAC14, whilst the others received OAM14. The 13C-urea breath test was performed before randomization and 4–5 weeks after eradication therapy.Results : In the intention-to-treat analysis, the eradication rates for empirical therapies were as follows: OAC7, 47.4% (27/57); OAC14, 34.5% (20/58); OAM14, 63.2% (36/57); it was 74.3% (84/113) for the susceptibility-based treatment (P 〈 0.01 when compared with OAC7 and OAC14). In patients receiving clarithromycin, the eradication rates were 80% for clarithromycin-susceptible strains and 16% for clarithromycin-resistant strains; in patients receiving OAM14, the eradication rates were 81% for metronidazole-susceptible strains and 59% for metronidazole-resistant strains.Conclusions : Eradication rates of approximately 75% can be achieved with second-line triple therapy based on antibiotic susceptibility testing. If susceptibility testing is not available, OAM14 is an appropriate alternative.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2003.01759.x
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  • 4
    Electronic Resource
    Electronic Resource
    Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 5 (1991), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25 000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25 000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P 〈 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P 〈 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.1991.tb00040.x
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  • 5
    Electronic Resource
    Electronic Resource
    Does lansoprazole influence postprandial digestive function? (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 7 (1993), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of a potent proton pump inhibitor on postprandial digestive functions were compared with those of a placebo in a double-blind randomized crossover study. Six healthy male volunteers received 30 mg/day of lansoprazole or placebo for 7 days, with a wash-out period of 14 days. As compared to placebo, lansoprazole induced a marked decrease of mean ± S.E.M. 3-h gastric acid secretion from 46.8 ± 10.8 mmol to 10.9 ± 2.5 mmol (P 〈 0.05), and a decrease of the volume of gastric contents emptying into the duodenum from 1043 ± 139 ml to 660 ± 87 ml (P 〈 0.05). However, gastric emptying remained unchanged with meal gastric emptying half times of 66 ± 5 min and 67 ± 13 min, respectively. During the 3-h postprandial period, duodenal lipase and chymotrypsin outputs were 366 ± 123 KIU and 56 ± 11 KIU with lansoprazole and 436 ± 119 KIU and 49 ± 8 KIU with placebo (N.S.). Bile acid outputs were 5.3 ± 0.7 mmol and 6.0 ± 1.0 mmol, respectively (N.S.) There was no change in kinetic profiles of biliarypancreatic secretion. We conclude that potent inhibition of gastric secretion by chronic administration of a proton pump inhibitor at usual therapeutic dose alters neither meal gastric emptying nor postprandial biliary-pancreatic secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.1993.tb00144.x
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  • 6
    Electronic Resource
    Electronic Resource
    Maintenance of gastric pH above 6 with intravenous famotidine in patients with a bleeding duodenal ulcer (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 9 (1995), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: The secondary prevention of bleeding from ulcers may be improved if antisecretory drugs are able to maintain a 24-h gastric pH close to neutral. Aim: To evaluate the effect of intravenous famotidine at a conventional dose of 40 mg/day on 24-h intragastric pH in patients with a bleeding duodenal ulcer, and to determine the dose required to maintain gastric pH 〉 6 by use of a Gastrojet (MIC, Switzerland) device (a pH meter-controlled programmable pump). Methods: Twelve patients (nine men, three women), aged 24–78 years, admitted for a bleeding duodenal ulcer, were studied after active bleeding had stopped for at least 6 h. Gastric pH was recorded for two consecutive 24-h periods, each starting at 16.00 hours. The patients were fasted during these periods and received an infusion of 2.5 L of isotonic glucose. They were given famotidine, as a continuous i.v. infusion of 40 mg during one period, and at a rate determined by the Gastrojet during the other period (in a random sequence), with the aim of maintaining the gastric pH above 6. Results: The 24-h median (interquartile range) pH and the mean (± S.E.M.) percentage of the 24-h period with a gastric pH 〉 6 were both significantly higher during the Gastrojet period than during the continuous infusion: 6.4 (6.3–6.5) vs. 5.7 (2.7–6.4) (P 〈 0.01) and 74±5% vs. 44 ± 7% (P 〈 0.002), respectively. The mean dose of famotidine delivered by the Gastrojet was 172 mg (range: 101–200 mg). The entire available amount of famotidine (200 mg) was delivered in four of the 12 patients. The percentage of time at pH 〉 6 (mean ± S.E.M.) was significantly higher at night (22.00 to 07.00 hours) than during the rest of the day (88 ± 2 vs. 70 ± 6%; P 〈 0.005) and the mean quantity of famotidine delivered per hour was significantly lower during the night (6.3 ± 0.8 mg/h vs. 8.4 ± 0.5 mg/h; P 〈 0.02). Conclusion: We conclude that 40 mg of famotidine delivered as a continuous i.v. infusion is not sufficient to maintain gastric pH 〉 6 for 24 h in duodenal ulcer patients. Our study with the Gastrojet device shows that it may be possible to achieve this goal by using a much larger dose, preferably delivered during the day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.1995.tb00370.x
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  • 7
    Electronic Resource
    Electronic Resource
    Impact of Helicobacter pylori resistance to clarithromycin on the efficacy of the omeprazole–amoxicillin–clarithromycin therapy (2001)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 15 (2001), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Helicobacter pylori resistance to clarithromycin is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor–amoxicillin–clarithromycin (proton pump inhibitor–AC) therapy, which is the first-line regimen in France.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To determine the respective effects of clarithromycin primary and secondary resistances on efficacy of the proton pump inhibitor–AC regimen and to determine whether failures are associated with persistence of the same strain or with emergence of a new one.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:A total of 123 H. pylori-infected patients were treated for 7 days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. Minimal inhibitory concentrations of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The pre-treatment and post-treatment prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79% (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection. Resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In our hospital, failures of the proton pump inhibitor–AC therapy are related to both clarithromycin primary and secondary resistances, but the emergence of secondary resistance does not explain all of the failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2001.00971.x
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  • 8
    Electronic Resource
    Electronic Resource
    One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease (2000)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 14 (2000), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85–94%) and 91% (86–94%); OAC, 88% (82–92%) and 91% (86–95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2000.00911.x
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  • 9
    Electronic Resource
    Electronic Resource
    Twenty-four-hour intragastric acidity and plasma gastrin during 3-month treatment with omeprazole in healthy subjects (1997)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Prolonged treatment with omeprazole 20 or 40 mg/day is sometimes required, especially for severe oesophagitis. However, information about long-term effects on intragastric acidity and plasma gastrin response with such drug regimens is scarce. Methods: Sixteen healthy subjects (11 men, 5 women, mean age 29 years) randomly received either 20 or 40 mg of omeprazole once daily (at 08.00 h) for 3 months. Gastric pH was recorded every 6 s for 24 h from noon to noon under standardized conditions, and blood samples were collected hourly in order to determine the 24-h plasma gastrin response on day 0 (pre-entry), day 7, day 28 and day 90. Results: From day 0 to day 7, 24-h median pH increased from 1.7 to 4.6 and mean percentage of time at pH 〈 4 decreased from 89% to 35% with omeprazole 20 mg. Respective values with omeprazole 40 mg were 1.9 to 4.3, and 89% to 34%. Inhibition of gastric acidity remained unchanged during the 3 months of treatment. Despite similar effects on the basis of 24-h analysis, the decrease in daytime acidity was slightly higher with omeprazole 40 mg than with omeprazole 20 mg. Twenty-four-hour integrated plasma gastrin significantly increased with both drug regimens between day 0 and day 7 (P 〈 0.01), and between day 7 and day 28 (P 〈 0.01) with omeprazole 40 mg; there was no significant increase between day 28 and day 90 with either of the drug regimens. Conclusion: Omeprazole 20 and 40 mg/day provides long-term stable acid suppression with a progressive increase in gastrin response, stabilizing after 2 months of treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.1997.00182.x
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of low-dose rabeprazole and omeprazole on gastric acidity: results of a double blind, randomized, placebo-controlled, three-way crossover study in healthy subjects (2004)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : The treatment of acid-related symptoms requires rapid and consistent acid suppression, especially with on-demand regimens.Aim : To compare the antisecretory activity of low-dose rabeprazole and omeprazole in healthy, Helicobacter pylori-negative subjects.Methods : In this randomized, double-blind, placebo-controlled, three-way crossover study, 27 volunteers were given rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10–14-day washout between treatments. Intragastric pH was monitored for 24-h on days 1 and 7 of each treatment.Results : Median gastric pH was significantly higher with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3, respectively (P = 0.0056, rabeprazole vs. omeprazole; P 〈 0.0001, rabeprazole vs. placebo); day 7: 3.7, 2.2 and 1.3, respectively (P = 0.0016 rabeprazole vs. omeprazole; P 〈 0.0001, rabeprazole vs. placebo). Time with gastric pH above 4 was significantly higher with rabeprazole than with omeprazole: day 1, 5.8 h vs. 3.7 h, respectively (P 〈 0.02); day 7, 10.5 h vs. 4.6 h, respectively (P = 0.0008).Conclusions : Rabeprazole 10 mg provides more rapid acid inhibition compared with omeprazole 10 mg. After 7 days, the time with pH above 4 is more than doubled with rabeprazole 10 mg vs. omeprazole 10 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.02176.x
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