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Biomedical subjects

G Treiber

Publications and source records attributed to G Treiber.

36 records · Page 2Linked to original sources
PubMed1998

Amoxicillin/metronidazole/omeprazole/clarithromycin: a new, short quadruple therapy for Helicobacter pylori eradication.

BACKGROUND: Triple therapy regimens including two antibiotics plus acid suppression have become the new standard therapy in Helicobacter pylori eradication because of success rates of about 90%. However, these regimens are still costly, duration is about one week or less, and side-effects are not negligible. We therefore evaluated a new quadruple therapy, because theoretically a shorter duration of treatment may result in reduced costs, fewer side-effects, and possibly in a lower potential for antibiotic resistances. METHODS: Controlled, prospective pilot study including H. pylori-positive patients with gastric or duodenal ulcers or erosive gastritis, treated after failure of dual therapy (proton-pump-inhibitors or ranitidine plus amoxicillin) or for the first time. They were assigned to a one week triple standard therapy, consisting of metronidazole 400 mg bid + omeprazole 20 mg bid + clarithromycin 250 mg bid, or a newly created quadruple-regimen, which adds amoxicillin (1 g bid) to the above triple regimen. Each of the four drugs was given for 5 days. H. pylori status was checked by 13C urea breath test before and after four weeks of therapy. RESULTS: A total of 71 patients were treated by quadruple therapy, and 42 patients were treated by triple therapy. The eradication rate of H. pylori for patients under quadruple treatment, without vs. with previous dual therapy, were 96% vs. 92% (42/44 vs. 22/24) by per protocol and 91% vs. 88% (42/46 vs. 22/25) by intention to treat analysis (comparisons not significant). No major side-effects were reported. CONCLUSIONS: Five-day quadruple therapy (with omeprazole, metronidazole, clarithromycin and amoxicillin) represents an effective and safe new regimen for H. pylori eradication.

Adolescent↗
PubMed1998

The impact of Helicobacter pylori eradication on peptic ulcer healing.

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Age-dependent eradication of Helicobacter pylori with dual therapy.

BACKGROUND: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. METHODS: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. RESULTS: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 +/- 1.7; 51 +/- 25%) than for omeprazole (5.4 +/- 1.1: 77 +/- 25%; P < 0.05) or lansoprazole (4.4 +/- 1.6: 68 +/- 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 +/- 13 years) than patients still H. pylori-positive (47 +/- 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75-83%) in subgroups of patients (> 50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. CONCLUSION: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Omeprazole, amoxicillin and bismuth for peptic ulcer healing and Helicobacter pylori eradication.

A controlled, randomized study was performed in patients with active peptic ulcer disease and positive Helicobacter pylori (Hp) status to assess the clinical efficacy (endoscopic healing and eradication of Hp) of different combined treatments. In the first part of the study a treatment with omeprazole (CAS 73590-58-6) (40 mg once daily) alone (group A) or in combination with tripotassium dicitrato bismuthate (TDB; 240 mg bid, group B) for 4 weeks was evaluated in 20 and 13 patients, respectively. As expected healing rates were high and comparable (75 vs. 85%), however, Hp-eradication was zero in both groups. In the subsequent second part of the trial group A (n = 19) received omeprazole (20 mg bid) for 2 weeks + amoxicillin (CAS 26787-78-0) tablets (1 g bid only 2nd week). Accumulated healing rate increased to 95% but Hp-eradication was 37%. From group B only 8 patients participated in a second 4-week course of monotherapy with TDB. Whereas healing occurred in all individuals, Hp-eradication was still low (12.5%). In addition plasma levels (omeprazole, Bi) and urinary excretion (Bi) were monitored to test whether drug interaction and/or noncompliance of the patients could help to explain the clinical findings. Systemic availability of Bi was increased by the coadministration of omeprazole and plasma levels of omeprazole were in general higher in Hp-positive patients if compared to those of Hp-negative patients. The following conclusions could be drawn from the 4 parts of the study: Treatment of peptic ulcer disease with omeprazole either alone or in combination with TDB is effective for ulcer healing but not for eradicating Hp. Omeprazole seems to decrease the Hp-eradicating potential of Bi probably due to a drug interaction. A second treatment course with TDB is apparently not of much benefit. One week pretreatment with omeprazole does not affect healing but might attenuate Hp-eradication rate of subsequent combined treatment with amoxicillin. One week coadministration of amoxicillin is not sufficient. The magnitude of omeprazole's plasma levels has no effect on Hp-eradication rates. As the numbers of patients in this study was relatively small these conclusions need to be confirmed by larger trials.

Adult↗
PubMed1996

The influence of drug dosage on Helicobacter pylori eradication: a cost-effectiveness analysis.

OBJECTIVES: This review provides an updated overview on Helicobacter pylori (HP) trials, focusing on drug dosage and cost:benefit ratio. METHODS: Literature review, with analysis of 362 treatments with 13,562 patients. RESULTS: Statistical evaluation demonstrated the following mean HP eradication rates (ER): 11.7% for monotherapy, 50.7% for dual therapy without acid suppression, 59.8% for dual therapy including acid suppression, 78.1% for triple therapy without acid suppression, 77.5% for triple therapy including acid suppression, and 89.1% for multiple combination therapy (differences between all groups, p < 0.001). In dual therapy, omeprazole/amoxicillin or clarithromycin (mean ER 65.9 vs. 67.6%, NS) showed better results than other combinations. Favorable results in triple therapy were achieved by combined bismuth/imidazoles/tetracycline or by omeprazole/imidazoles/amoxicillin or clarithromycin (mean ER 83.4 vs. 83.5% vs. 93%, NS). The best mean eradication rate, 93.5%, was attained with omeprazole/bismuth/imidazoles/tetracycline. Subgroup analysis revealed a significant correlation between the dose/duration of therapy and the ER for most combinations. The best cost:benefit ratio was demonstrated for omeprazole/imidazoles/clarithromycin (triple therapy including acid suppression). CONCLUSIONS: The optimal cost:benefit ratio will be achieved by treatment for 1 wk with omeprazole (20 mg/day), imidazoles (such as metronidazole 2 x 400 mg/day), and clarithromycin (2 x 250 mg/day). If dual therapy is taken into account in terms of simplicity and few side effects, the treatment success in the combination of omeprazole ( > or = 2 x 20 mg/day) and amoxicillin ( > or = 2 g/day) or clarithromycin ( > or = 1 g/day), each given for 2 wk, is highly dependent on optimal drug dosage.

Amoxicillin↗
PubMed1994

Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate.

OBJECTIVE: Omeprazole is an effective drug for treating active peptic ulcer, whereas tripotassium dicitrato bismuthate can prevent ulcer relapse if Helicobacter pylori is eradicated. Because both drugs will be given concomitantly, drug interactions have to be considered, especially since absorption of bismuth may be dependent on intragastric pH, which will be elevated by omeprazole. METHODS: In a placebo-controlled crossover study, six healthy volunteers received daily oral doses of 40 mg omeprazole for 1 week and a single oral dose of 240 mg tripotassium dicitrato bismuthate. Plasma concentration-time profiles (AUC) and urinary excretion (Ae) of bismuth were measured by atomic absorption spectrophotometry and plasma levels of omeprazole by HPLC. In addition, intragastric pH values were monitored for 8 hours. RESULTS: As expected, control mean pH values (2.1) were evaluated to 4.7 by omeprazole (p = 0.001), which was eliminated with a half-life of 1.3 +/- 0.7 hours (mean +/- SD) and an oral clearance of 387 +/- 221 ml/min. The increase of intragastric pH was related to the AUC of omeprazole (r = 0.89; p = 0.017). Omeprazole increased absorption of bismuth because AUC and Ae were higher (p < or = 0.05) during omeprazole treatment (172 +/- 158 micrograms/L.hr and 1.9 +/- 2.0 mg/8 hr, respectively) compared with placebo (46 +/- 33 micrograms/L.hr and 0.27 +/- 0.28 mg/8 hr, respectively). A significant correlation (r = 0.85; p = 0.038) could be observed between intragastric pH differences and Ae values. CONCLUSIONS: Omeprazole caused an increase of the systemic availability of bismuth from tripotassium dicitrato bismuthate. Whether this pharmacokinetic interaction between both drugs results in alterations of H. pylori eradication or the toxic potential of bismuth remains to be elucidated by further clinical studies.

Administration, Oral↗
PubMed1993

Disposition of ibuprofen in patients with liver cirrhosis. Stereochemical considerations.

Following a single oral dose of racemic ibuprofen 600mg the stereoselective disposition of its enantiomers was studied in 8 patients with moderate to severe cirrhosis. Compared with the elimination half-life (t1/2) of (-)-R- and (+)-S-ibuprofen in 8 healthy age-matched controls (1.7 +/- 0.3h and 1.8 +/- 0.5h, respectively), t1/2 was prolonged significantly (p < 0.045 and < 0.001, respectively) in patients with cirrhosis (t1/2 = 3.1 +/- 1.7h and 3.4 +/- 1.0h, respectively). Whereas the low amounts excreted unchanged into urine differed slightly in both groups studied, much less (p < 0.01) conjugated ibuprofen was recovered either as the R-enantiomer (0.9 +/- 0.4% vs 4.1 +/- 2.8% of the dose) or the S-enantiomer (6.4 +/- 2.5% vs 26.5 +/- 12.9% of the dose) in patients with cirrhosis. Metabolic inversion of the inactive (-)-R-ibuprofen to the active (+)-S-ibuprofen may be impaired in hepatic dysfunction since the normal ratio of areas under the curve (AUC) for R- and S-enantiomers (0.79 +/- 0.18) was significantly (p < 0.02) higher in patients with cirrhosis (1.10 +/- 0.28). In a second study, a single oral dose of 400mg (+)-S-ibuprofen was administered to 8 healthy volunteers and 8 patients with cirrhosis. Elimination of this enantiomer was slightly impaired as could be seen from the prolonged t1/2 (1.6 +/- 0.1h vs 2.6 +/- 0.5h; p < 0.001) and the increase in AUC (101 +/- 35 vs 144 +/- 41 mg/L.h; p = 0.041). In conclusion, in patients with liver disease, hepatic elimination of ibuprofen is impaired. This should be taken into consideration especially if the racemic drug is used. Direct administration of the active (+)-S-enantiomer seems to offer less vulnerable treatment.

Adult↗
PubMed1991

Tripotassium dicitrato bismuthate: absorption and urinary excretion of bismuth in patients with normal and impaired renal function.

We 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 micrograms/L) reached within about 30 to 40 min, absorbed and plasma 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 micrograms/L to 15 micrograms/L (normal renal function) or to 20-25 micrograms/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 less than or equal to 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 treatment is anticipated.

Absorption↗
PubMed1991

Effect of omeprazole on nocturnal intragastric pH in cirrhotics with inadequate antisecretory response to ranitidine.

Failure of acid suppression by H2-receptor antagonists has been observed, and recently we have found a higher frequency of patients with inadequate antisecretory response among patients with cirrhosis of the liver. In the present study comprising 16 cirrhotics with inadequate antisecretory response to 300 mg of ranitidine, we tested the effect of 40 mg omeprazole. Nighttime intragastric pH was continuously monitored, and a rise in the intragastric pH above 4.0 for more than 6 h following the oral dose at 18.00 h was considered as response. The median pH profile during the omeprazole treatment was significantly higher than with ranitidine (p less than or equal to 0.001). In contrast to 300 mg ranitidine, which despite sufficient plasma levels 2 and 4 h after intake (762 +/- 431 and 802 +/- 668 ng/ml) resulted in a rise in the nighttime intragastric pH above 4 only for 1.8 +/- 1.7 h, after omeprazole for at least 5 days, the intragastric pH was for 10.1 +/- 2.4 of 12 h above 4 during the night (p less than 0.001). The omeprazole plasma levels were 611 +/- 323 and 881 +/- 533 ng/ml after 2 and 4 h. The data obtained with intragastric pH monitoring indicate that the H+K(+)-ATPase inhibitor omeprazole is able to overcome the H2-blocker resistance in cirrhotics.

Female↗
PubMed1991

Addition of misoprostol to ranitidine in non-responders to H2-blockers and pirenzepine.

In the present study, which comprised 14 patients in whom 300 mg and 900 mg of ranitidine as well as in combination with pirenzepine had failed to suppress acid secretion, we tested the effect of adding misoprostol. Night-time intragastric pH was continuously monitored, a rise in the intragastric pH above 4.0 h more than 6 h following the oral dose at 18.00 h being considered a response. In only 1 of the 7 patients with cirrhosis, and in 1 of the 7 control patients, did the combination of 300 mg ranitidine and 400 micrograms of misoprostol result in sufficient acid suppression. Mean pH profiles during the four study periods were not significantly different and the effect of misoprostol was similar in cirrhotics and controls. The inefficacy of the addition of misoprostol in this selected group of patients who did not respond even high doses of ranitidine (+/- pirenzepine) does not favour the hypothesis that gastric mucosal prostaglandin efficiency may be an important factor in the non-response to H2-receptor antagonists. It appears unlikely that the cause is localized solely at the site of H2-receptors.

Alprostadil↗
PubMed1990

Gastric emptying in non-responders to H2-receptor antagonists.

H2-receptor antagonists are known to fail to increase the intragastric pH in some patients (so-called non-responders), and we have recently found a higher frequency of non-responders among cirrhotics. Since intragastric pH is also affected by gastric emptying, in the present study we determined the gastric emptying of 300 ml orange juice labelled with [99mTc]-Solco Nanocoll using a gamma camera. Measurements were made over a period of 60 min in cirrhotic patients and controls without liver disease who either responded to 300 mg ranitidine or showed no response. The mean (+/- SD) liquid half-emptying time (T1/2) was 26.3 +/- 17.5 min (range, 9-75 min) in responders (n = 10), 20.9 +/- 8.6 min (range, 7-34 min) in non-responders (n = 10), 19.4 +/- 19.2 min (range, 7-75 min) in cirrhotics (n = 11), and 27 +/- 4.6 min (range, 17-33 min) in controls (n = 9). In 19 of the 20 subjects gastric emptying was normal (T1/2, less than 40 min). Since gastric emptying was not delayed in any of the non-responders, it would appear very unlikely that gastric motility plays a major role in the non-response to H2-receptor antagonists.

Adult↗
PubMed1990

Is cyclosporin A an inhibitor of drug metabolism?

1. The potential for a drug interaction between cyclosporin A and midazolam was investigated since both compounds appear to be metabolized by the same cytochrome P-450 isoenzyme. 2. In vitro evaluation of the binding of cyclosporin A to rat microsomal cytochrome P-450 indicated a Ks-value of 0.4 microM. In further studies with rat liver microsomes IC50-values of 6, 8 and 70 microM cyclosporin A were determined for the inhibition of the metabolism of midazolam to its alpha-OH-,4-OH- and di-OH-metabolites, respectively. 3. Comparative studies with human liver microsomes indicated IC50-values of approximately 300 microM for the formation of alpha-OH-midazolam and of 65 microM for the formation of 4-OH-midazolam. 4. The pharmacokinetics of a single intravenous dose of midazolam (0.075 mg kg-1) was studied in nine patients receiving cyclosporin A to prevent rejection of their transplanted kidneys. The average steady state blood concentrations of cyclosporin A, measured by r.i.a. using a specific monoclonal antibody, varied during a dosing interval between 175 and 600 ng ml-1. 5. In these patients the hepatic elimination of midazolam was characterized by a mean t1/2 (+/- s.d.) of 2.3 +/- 1.2 h and a plasma clearance (CL) of 414 +/- 95 ml min-1. These values were not different from those of normal human subjects (t1/2 = 1.5 to 4 h, CL = 350 to 700 ml min-1). 6. From the results of the in vitro experiments it is concluded that cyclosporin A may potentially inhibit drug metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1971

Biochemical characterization of a mutant isoleucyl-transfer ribonucleic acid synthetase from Escherichia coli K-12.

Isoleucyl-transfer ribonucleic acid (tRNA) synthetase [l-isoleucine: soluble RNA ligase (adenosine monophosphate), EC 6.1.1.5; IRS] was partially purified from Escherichia coli K-12 and from an ileS mutant that appears to be altered in IRS. The half-life of wild-type IRS, incubated at 60.5 C, is 69 min, whereas that of mutant IRS is 8 min. Mutant IRS shows about a 100-fold lower affinity than wild-type IRS for isoleucine, dl-valine, thiaisoleucine, and O-methyl-dl-threonine, both in the pyrophosphate exchange assay and in the assay of isoleucyl-tRNA formation. The affinity of the mutant enzyme for adenosine triphosphate in the assay of isoleucyl-tRNA formation is 15-fold lower than that of the wild-type enzyme. The affinity of mutant IRS for tRNA is not changed as compared with wild-type IRS. These data show that mutant IRS has an altered structure and clearly confirm that ileS is the structural gene for IRS.

Adenosine Triphosphate↗