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Biomedical subjects

R Gugler

Publications and source records attributed to R Gugler.

At least 91 records · Page 5Linked to original sources
PubMed1982

Gastric acid inhibition and oxmetidine kinetics in duodenal ulcer.

Gastric acid inhibitory effects and kinetics of oxmetidine, a new histamine H2-receptor antagonist, were examined in five patients with duodenal ulcer disease. A constant intravenous infusion of impromidine was used to stimulate gastric acid secretion for 6 hr. Oxmetidine was then given in a 28-mg IV infusion and a 200-mg oral solution. The maximum inhibition of gastric acid output was, on average, 77% after infusion and 92% after oral doses, with similar values for volume inhibition. Mean overall percent inhibition of acid output, volume, and H+ concentration was 22%, 8%, and 15% for the intravenous dose and 51%, 33%, and 29% for the oral dose. The effect lasted for 3 hr after the intravenous dose and for 5 hr after the oral dose. Mean values for systemic clearance and half-life were 161 ml/min and 2.3 hr. An average of 4.3% of the dose was recovered in urine as unchanged drug and 27% was recovered as a glucuronide metabolite. Mean bioavailability was 36%. Plasma concentration for 50% inhibition of acid output was 0.50 microgram/ml, indicating that oxmetidine is 2.5 times as potent as cimetidine. No adverse effects were noted during the study.

Adult↗
PubMed1982

Altered disposition and availability of cimetidine in liver cirrhotic patients.

1 The pharmacokinetics and bioavailability of cimetidine were studied after 200 mg oral and intravenous doses in 14 patients with liver cirrhosis, and results were compared to a control group of 12 ulcer patients. 2 In cirrhotic patients, the volume of the central compartment (0.41 +/- 0.06 v 0.19 +/- 0.09 1/kg) and the volume of distribution at steady-state (1.02 +/- 0.17 v 0.80 +/- 0.24 1/kg) were significantly increased. No differences were observed in the area volume of distribution, the total systemic plasma clearance and renal clearance. The non-renal clearance was significantly decreased from 191 +/- 46 to 123 +/- 102 ml/min. 3 The bioavailability of cimetidine (area method) was significantly increased from 60 +/- 23% to 77 /+- 18% in the cirrhotic patients. Also increased was the time during which plasma levels exceeded 0.5 microgram/ml. 4 Urinary excretion of cimetidine was increased in liver cirrhosis by 32% after intravenous and by 36% after oral administration, while the amount of the sulphoxide metabolite decreased accordingly. Creatinine clearance in the cirrhotic patients was highly correlated with the renal clearance of cimetidine as well as its total plasma clearance.

Adult↗
PubMed1982

Effect of smoking on duodenal ulcer healing with cimetidine and oxmetidine.

The effect of oxmetidine 800 mg/day, a new histamine H2-receptor antagonist, on duodenal ulcer healing was compared with cimetidine 1000 mg/day in a two-centre double-blind trial. Ninety-nine patients completed the study. After four weeks, ulcers were healed in 74% of the cimetidine-treated patients and in 78% of the oxmetidine-treated patients (p greater than 0.05). Healing rates after eight weeks increased to 90% in the cimetidine group and to 94% in the oxmetidine group. Healing rates after four weeks were, however, different in the two centres (p less than 0.01): in centre 1 88% of the cimetidine-treated, but 63% of the oxmetidine-treated patients healed, in centre 2 rates were 60% (cimetidine) and 92% (oxmetidine). Analysis of patient data revealed that in the two centres treatment success was inversely correlated (p less than 0.01) with the percentage of smokers in each treatment group. Smoking significantly influences duodenal ulcer healing with histamine H2-receptor antagonists.

Adult↗
PubMed1981

A prospective randomised trial on the effect of monitoring plasma anticonvulsant levels in epilepsy.

To evaluated whether knowledge of plasma levels of anti-epileptic drugs has an effect on therapeutic outcome, 127 epileptic outpatients were randomly assigned to two groups (A and B). Plasma levels of group A were reported to the treating physician who attempted to keep the plasma levels within the "therapeutic range." The treating physician was not informed of the results of plasma level determinations of group B. Data from 105 patients were available for assessment at the end of the study year. Therapeutic results of groups A and B were not significantly different. The reduction in seizure frequency was associated with an increase in plasma concentrations of the anti-epileptic drugs. Thus, under the conditions of the study, knowledge of plasma levels of anti-epileptic drugs did not further improve therapeutic results.

Anticonvulsants↗
PubMed1981

Influence of phenobarbital treatment on cimetidine kinetics.

The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase of nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P less than 0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P less than 0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.

Adult↗
PubMed1981

Impaired cimetidine absorption due to antacids and metoclopramide.

In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hydroxide containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P less than 0.01) reduced the bioavailability (area under the plasma level-time curve) of cimetidine, on average by one third. Metoclopramide also reduced the bioavailability by an average of 22%. The reductions were associated with significantly reduced excretion of cimetidine in urine. There was no change in the half-life or renal clearance of cimetidine, supporting the hypothesis of reduced gastrointestinal absorption. The results indicate that cimetidine and antacids should not be given together, and that the dose of cimetidine may have to be increased if it is administered concomitantly with metoclopramide.

Adult↗
PubMed1981

Cimetidine plasma concentration-response relationships.

Cimetidine plasma concentration-response relationships were investigated in six healthy subjects using suppression of gastric acid secretion under continuous pentagastrin stimulation (1.5 micrograms/kg/hr) as a test model. With the Hill equation the sigmoid was preferable to the linear relationship between plasma concentration and effect, and there were significant correlations of 0.78 micrograms/ml (range 0.54 to 1.04 micrograms/ml) for 50% inhibition of gastric acid secretion was determined; mean concentration for 90% inhibition was calculated to be 3.9 micrograms/ml. The model described should allow determination of whether different patient populations (e.g., healthy subjects, patients with ulcers, male and female patients, patients with renal or liver disease) differ from one another in concentration-response relationships to histamine H2-receptor antagonists, so that appropriate drug plasma levels should be achieved for specific degrees of inhibition of gastric acid secretion.

Adult↗
PubMed1981

[Drug dosing in chronic hepatic disease (author's transl)].

Disposition of drugs, which are primarily metabolized by the liver, will be influenced in chronic liver disease by the following factors: intrinsic clearance, liver blood flow, and shunt volume. This group of drugs may be divided in two subgroups: (a) drugs with a high clearance, a high extraction rate and a short biological half-time, and (b) drug with a low clearance, a low extraction rate, and a long biological half-time. A high extraction rate means a low systemic bioavailability, since a rather big proportion of the drug will be eliminated after oral intake already during the first pass through the liver (= first past effect). In liver cirrhosis bioavailability may be increased manifold because of the portosystemic shunting. Thus there is the danger of overdosage in group (a) drugs because of two mechanisms: reduced elimination and increased bioavailability.

Biological Availability↗
PubMed1980

[Absolute bioavailability of theophylline (Euphylline)].

The pharmacokinetics and bioavailability of theophylline have been investigated in eight healthy subjects following application of the drug in form of a tablet, a retard tablet (enteric-coated), and a suppository (Euphyllin) in comparison with an intravenous preparation. Peak plasma concentrations were measured 1.5 hours (tablet), 6 hours (retard tablet) and 4 hours (suppository) after drug administration, respectively. The absolute bioavailability was of th tablet 105 +/- 25%, of the retard table 81 +/- 23%, of the suppository 74 +/- 25%. The variations observed were primarily due to variations in the other pharmacokinetic parameters, only to a lesser extent to variable absorption of theophylline.

Adult↗
PubMed1980

[Bioavailability of cimetidine after partial gastrectomy (author's transl)].

Absorption characteristics of cimetidine were studied in 10 patients after Billroth I and 12 patients after Billroth II gastrectomy and compared with 9 patients without gastric disease. The onset of absorption after 400 mg cimetidine was identical in all groups, but peak plasma concentrations occurred somewhat (18%) later in B I and significantly (42%) later in B II patients (p less than 0.05). Plasma half life was not different between the 3 groups. The area under the plasma level curve as a measure for bioavailability was significantly increased in the two gastrectomy groups (17% and 23%, resp.). In addition, the duration of effective plasma concentrations above 0.5 microgram/ml was significantly prolonged in the two groups.

Biological Availability↗
PubMed1980

Comparative pharmacodynamics and plasma levels of beta-adrenoceptor blocking drugs.

1. Metoprolol (ME), pindolol (PI) and propranolol (PR) were studied in nine subjects at different doses and at 'maximum beta-adrenoceptor blockade' at a defined exercise load. Exercise tests were performed after each dosing period; isoprenaline stimulation was studied at the highest dose level. 2. ME and PR reduced heart rate at rest with most doses tested, while PI had no effect on resting heart rate. 3. Exercise heart rate was reduced with the smallest daily doses (ME 75 mg; PI 7.5 mg; PR 60 mg), and maximum reduction was from 163 to 116 beats/min (ME), 124 (PT) and 115 (PR) beats/min with daily doses of 242, 23 and 233 mg, respectively. 4. Resting blood pressure was not significantly affected by any beta-adrenoceptor blocker dose, but exercise induced blood pressure decreased from 166 to 130 (ME), 138 (PI) and 131 (PR) mm Hg, respectively. 5. Mean plasma concentrations at 'maximum beta-adrenoceptor blockade' were 158 (ME), 24 (PI) and 159 (PR) ng/ml without significant differences in the plasma level variation between beta-adrenoceptor blockers. 6. Isoprenaline doses required to increase heart rate by 30 beats/min were 3.8 microgram (control), 22 microgram (ME), 458 microgram (PI) and 200 microgram (PR), respectively. The differences may be due to different ratios of beta 1, beta 2 activity of the beta-adrenoceptor blockers tested.

Adrenergic beta-Antagonists↗
PubMed1980

[Early cancer and chronic erosions with foveolar hyperplasia of gastric mucosa (author's transl)].

A case report is given of a patient with an early gastric carcinoma (IIa + IIc), who had at the same time chronic erosions, accompanied by a reactive foveolar hyperplasia of the mucosa as could be demonstrated after surgery. A causal relationship of these lesions has not yet been proven, coincidence of the changes seems to be rare as judged from the literature. Nevertheless this case would suggest, that in patients with chronic gastric erosions each lesion should be carefully controlled throughout the course of the disease.

Adenocarcinoma↗
PubMed1979

Cimetidine for anastomotic ulcers after partial gastrectomy. A randomized controlled trial.

In a randomized double-blind multicenter trial, 15 outpatients with endoscopically proved anastomotic ulceration after Billroth I or Billroth II partial gastrectomy received cimetidine, 1 g daily over eight weeks, or a placebo. All patients also received antiacid. The ulcer healed completely in all seven cimetidine-treated patients and in one of the eight placebo-treated patients (P less than 0.01). Ulcers not healed during the double-blind phase of the trial were all subsequently healed on open cimetidine treatment. There was a trend toward improvement of daytime symptoms in favor of cimetidine (P = 0.06), and nighttime symptoms were significantly relieved during the initial four weeks of cimetidine treatment P = 0.02). We conclude that cimetidine, 1 g daily, promotes healing of anastomotic ulcers after partial gastrectomy.

Adult↗
PubMed1979

[Antiepileptic therapy with valproinic acid. Correlations of side effects and serum levels of valproinic acid].

The side effects and possible side effects of the therapy with valproic acid were documented in 66 outpatients with epilepsy over a period of one year. The serum levels of valproic acid were measured gaschromatographically over the same period. The majority of the patients received a combined medication. The occurrence of side effects or possible side effects of valproic acid led to a dosage reduction of discontinuation of the compound in 25% of the patients. Patients complaining of tiredness showed significantly higher serum valproic acid levels than patients without clinical side effects. The other comparisons between the serum valproic acid levels in the case of clinical side effects and changes in laboratory findings and the serum levels of patients without side effects or changes in laboratory findings did not indicate a definite difference.

Acne Vulgaris↗