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Biomedical subjects

E Nüesch

Publications and source records attributed to E Nüesch.

34 records · Page 2Linked to original sources

Non-migrainous headache for the evaluation of oral analgesics.

1 Eight double-blind, randomized, placebo-controlled, single-dose, cross-over studies were carried out to evaluate the usefulness of testing the acute analgesic effect of drugs in out-patients with non-migrainous headache. 2 The reference compounds were either (1) aspirin, (2) a combination of aminopyrine, caffeine and butalbarbital (Optalidon), and (3) a combination of (2) with dihydroergotamine (Tonopan). 3 The test compounds were (1) proquazone, (2) fluproquazone and (3) and (4), new formulations of Optalidon and Tonopan in which the aminopyrine was replaced by propyphenazone. They were all found to be active. 4 A significant, dose-response relationship was established for aspirin (250, 500 and 1000 mg). 5 It is concluded that the non-migrainous headache model is a practical, reproducible and sensitive method for the investigation of the acute efficacy of analgesics.

Administration, Oral↗

A double-blind trial of synthetic salmon calcitonin in the treatment of acute pancreatitis.

A multicenter randomized double-blind trial on the use of synthetic salmon calcitonin (SCT) was carried out in 94 patients with acute pancreatitis. In addition to strict standard treatment--without aprotinin, atropine, or antacids--50 patients received daily 3 x 20 micrograms = 300 MRCU SCT intravenously and 44 patients received placebo for 6 days. Mortality rate was not influenced, overall mortality being 5.3%. The number of patients without pain and with normalized serum amylase on a given day was significantly higher in the group treated with SCT. Other parameters such as doses of analgesics, leukocyte count, and normalization of seven defined clinical and laboratory criteria within 6 days showed a positive trend without reaching significance.

Acute Disease↗

Absolute bioavailability of digoxin tablets.

Ten healthy male volunteers each received 0.5 mg digoxin orally and i.v. in a randomised, cross-over sequence with at least two weeks between doses. Plasma concentration and cumulative urinary excretion of digoxin were measured up to 6 and 144 h, respectively, after administration using a radioimmunoassay method. Absolute bioavailability (i.e. the percentage absorption from tablets compared to i.v. injection) was calculated by four methods: by comparing areas under plasma concentration/time curves (AUC) up to 6 h and to infinity, also by comparing cumulative urinary excretion up to 144 h (t max.) and to infinity. The mean of the two extrapolated values for the absolute bioavailability of digoxin (Sandoz) tablets is 78%.

Administration, Oral↗

Comparative pharmacokinetic investigations with tritium-labeled ergot alkaloids after oral and intravenous administration man.

Pharmacokinetic studies were carried out with nine tritium-labeled ergot alkaloids (dihydroergotmine, dihydroergotoxine, dihydroergostine, dihydroergocornine, dihydroergovaline, dihydroergonine, ergotamine, 1-methyl-ergotamine, and bromocriptine). Each drug was administered to 6 subjects in a randomized cross-over design as single oral and intravenous doses. Plasma levels and urinary excretion of tritium-labeled material were analyzed on a phenomenological basis by non-linear regression as a sum of exponentials. All substances showed the highest plasma concentration about 2 hours after oral administration (range 1.0-2.7 hours). The mean invasion half-life was 0.5 hours (range 0.32-1.12 hours). The mean elimination half-lives ranged from 1.4-6.2 hours for the alpha-phase and from 13 to 50 hours for the beta-phase, the longest values being observed with bromocriptine. From cumulative urinary excretion data after oral and after intravenous administration, a quotient of absorption was calculated. Values between 25 and 30% were found for most dihydrogenated drugs, namely dihydroergotamine, dihydroergotoxine, dihydroergostine, and dihydroergocornine, the only exceptions being dihydroergovaline and dihydroergonine, which were less well absorbed. Ergotamine and 1-methyl-ergotamine had an absorption quotient of about two-thirds and bromocriptine was nearly completely absorbed.

Administration, Oral↗

Pharmacokinetic study with synthetic salmon calcitonin (Sandoz).

18 patients randomly divided into 3 groups of six each received 35 mug (140 M.R.C. Units) of synthetic salmon calcitonin intravenously, intramuscularly or subcutaneously. Plasma and urin concentrations were determined using the radioimmunoassay method. There was a rapid distribution phase of ca. 12 minutes after intravenous injection then an elimination half-life of 1.1 hours. The volume of distribution was 11 litres. The invasion half-life after intramuscular and subcutaneous administration was 12 and 11 minutes respectively and the elimination half-lives 1 and 1.5 hours, respectively. The bioavailability of the intramuscular and subcutaneous forms was found to be 66 and 71% respectively when areas under their plasma concentration/time curves were compared with the intravenous area.

Adolescent↗

[Proceedings: Studies on the digoxin resorption in patients with decompensated right cardiac insufficiency].

Digoxin absorption was investigated in 7 patients suffering from severe right cardiac failure. After successful treatment and disappearance of the symptoms of right cardiac failure, the study was repeated in the same patients. Tritium-labelled digoxin in a dose of 0.1 mg as a solution, and non-labelled digoxin as a 0.25 mg tablet, were given to the patients in the fasting state. Blood samples were taken at specified time intervals up to 120 h and the urine was collected during the same period. The concentrations of digoxin in plasma and urine were measured in a liquid scintillation counter. The unlabelled digoxin was estimated by radioimmunoassay. The concentrations obtained in the plasma and urine were used to compute pharmacokinetic parameters. There was no significant difference in the plasma concentration curves in severe right cardiac failure and after successful treatment, nor did the calculated pharmacokinetic parameters differ significantly. Inhibition of digoxin absorption in severe right cardiac failure therefore seems unlikely.

Digoxin↗

Bioavailability studies with Digoxin-Sandoz and Lanoxin.

Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz tablets have been compared with Lanoxin manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to ""new'' Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.

Adult↗

Headache as a model for assessing mild analgesic drugs.

A method for the evaluation of the efficacy of mild analgesic drugs in outpatients with nonmigrainous headache is described. During the 3-hour drug evaluation period, patients were required to record at hourly intervals their pain intensity using both a verbal rating and a visual analog scale, their pain relief, and the occurrance of side effects. The results obtained in six studies consisted of comparisons of reference compounds aspirin (1000 mg) and two analgesic combinations (containing aminophenazone, caffeine, and butalbital); test medications aspirin (500 mg), codeine (30 mg), proquazone (300 mg), and new formulations of the two analgesic combinations (aminophenazone replaced by propyphenazone); and, in every study, placebo. In a seventh study, the analgesic effects of three doses aspirin (250, 500, and 1000 mg) were compared with that of placebo. Every study was conducted under double-blind, complete crossover conditions, and between 24 and 36 patients were used in each study. Using parametric and nonparametric statistical analyses, the reference compounds and the majority of the test medications exhibited significant analgesic properties. Also, a highly significant dose--response effect was demonstrated for aspirin. It is concluded that the headache model is a practicable, reliable, and sensisive method for the evaluation of the effectiveness of mild analgesic drugs.

Adult↗