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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 199 records · Page 11Linked to original sources
PubMed1978

Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus.

A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0.5-3.9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 mumol/l (244 mug/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs.Only 2 (5.4%) of the tolbutamide-treated patients and 10 (16.7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5.5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8.0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient.There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug.We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.

Adult↗
PubMed1978

Sympathetic innervation and noradrenaline content of normal human thyroid tissue from fetal, young, and elderly subjects.

In man, as well as in the mouse, there is morphologic and functional evidence for a direct, stimulatory influence of the sympathetic nervous system on the secretion of thyroid hormone by noradrenaline (NA), released from interfollicular adrenergic nerve terminals. In mice and rats, an age-related reduction of the sympathetic innervation of the thyoid has recently been observed. In the present study, possible age-related variations of the sympathetic innervation and the concentration of NA in human thyroid tissue were examined. Interfollicular adrenergic nerve terminals were studied by fluorescence histochemistry, and the tissue concentration of NA was measured by fluorometry. In apparently normal thyroid tissue, obtained from fetuses, young (20-45), and elderly (greater than 60) euthyroid people with thyroid cancer or hyperparathyroidism, the number of interfollicular adrenergic nerve terminals appeared to be reduced with increasing age, and the thyroid tissue concentration of NA was significantly lower in elderly than in young people. These findings may have functional importance.

Adult↗
PubMed1978

Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects.

The single-dose kinetics of D-propoxyphene, acetyl salicylic acid and phenazone, given in a combination tablet (Doleron), were compared in young and elderly subjects. Serial blood samples were taken 0--48 hours after administration. The plasma concentrations of propoxyphene and of its major metabolite, norporpoxyphene, were assessed by mass fragmentography, those of phenazone by gas chromatography, and those of acetyl salicylic acid plus salicylic acid by spectrofluorometry. Neither for propoxyphene, norpropoxyphene, acetyl salicylic acid nor phenazone did the areas under the concentration curves or the elimination half-lives differ between young and elderly subjects. These data do not provide pharmacokinetic support for a general reduction of the Doleron dosage in elderly subjects.

Administration, Oral↗
PubMed1978

Evaluation of spiramycin as a therapeutic agent for elimination of nasopharyngeal pathogens. Possible use of spiramycin for middle ear infections and for gonococcal and meningococcal nasopharyngeal carriage.

Varying doses of spiramycin were administered orally to healthy volunteers, and concentrations in serum and saliva were determined. The absorption of the drug was not significantly influenced by concomitant food intake. Saliva peak concentrations were 1.3--4.8 times higher than peak concentrations in serum. The elimination half life was 2--3 h in serum, and 4--8 h in saliva. Accumulation of the drug was seen in saliva but not in serum. The possible effect of spiramycin in eliminating bacteria from the nasopharynx was evaluated in vitro by comparing the spiramycin saliva concentrations with the MICs of bacteria known to establish themselves in the nasopharynx. At a concentration of 1.2 microgram/ml, spiramycin inhibited all investigated strains of group A streptococci, pneumococci and Branhamella catarrhalis, and at 2.4 microgram/ml all investigated gonococci. Concentrations of 19 and 38 microgram/ml, respectively, were required to inhibit all meningococci and Haemophilus influenzae. Following administration of 1.5 g spiramycin as a single daily dose for 3 days, the mean concentration in saliva reached or surpassed the MIC values of streptococci, pneumococci and Branhamella for 45 h, and of gonococci for 25 h. The possible use of spiramycin for prevention of relapses in acute otitis media and in treatment of serous otitis media is discussed, as well as the possible use of the drug in gonococcal and meningococcal nasopharyngeal carriage.

Acute Disease↗
PubMed1977

Bioavailability of metronidazole in fasting and non-fasting healthy subjects and in patients with Crohn's disease.

The possible influence of food intake on the bioavailability of metronidazole was examined in ten health volunteers by administration of a single dose of metronidazole on an empty stomach, and with a standardized breakfast. Food intake did not significantly alter the bioavailability of metronidazole. The interindividual variation in bioavailability appeared to be slight. In nine patients with Crohn's disease, the absorption of metronidazole appeared to be reduced and to be more variable than in healthy subjects. In both groups there was a clear relationship between the amount absorbed and dose/kg body weight. Thus, from the pharmacokinetic point of view, metronidazole can safely be given either with or between meals. The dose should be related to body weight.

Adult↗
PubMed1977

Enhancement by food of canrenone bioavailability from spironolactone.

The influence of food intake on the bioavailability of canrenone, the major and active metabolite of spironolactone, was explored in 8 healthy male volunteers. Spironolactone was administered as a single oral dose of 100 mg, both in the fasting state and together with a standardized breakfast. Numerous venous blood samples were taken from 30 min to 96 hr after ingestion of the drug, and the plasma concentrations of canrenone were determined by spectrofluorometry. The results indicate that more canrenone enters the general circulation when spironolactone in ingested together with a meal.

Administration, Oral↗
PubMed1977

Enhancement of hydralazine bioavailability by food.

The influence of food on the bioavailability of hydralazine in noncoated and coated tablets was examined in 5 healthy males. Each subject received an oral 50-mg dose on four different occasions: two 25-mg noncoated tablets with and without food and one 50-mg coated tablet with and without food. The meal was a standardized breakfast of 440 calories. Venous blood samples were obtained during a 6-hr period, and the plasma concentrations of unmetabolized hydralazine were assessed by a selective and sensitive gas chromatographic method. The results indicate that food enhances the bioavailability of hydralazine 2- to 3-fold both when noncoated and coated tablets are used.

Adult↗
PubMed1977

Enhancement of the bioavailability of propranolol and metoprolol by food.

The possible influence of food intake on the bioavailability of one nonselective and one cardioselective beta adrenoceptor antagonist, propranolol and metoprolol, was examined by serial determinations of the drug concentrations in blood of healthy subjects, taking single doses of the drugs both on an empty stomach and together with a standardized breakfast. The results indicate that food enhances the bioavailability of both propranolol and metoprolol. They also confirm that there is extensive interindividual variation in the bioavailability of these drugs.

Administration, Oral↗
PubMed1977

Effects of total energy withdrawal (fasting) on thelevels of growth hormone, thyrotropin, cortisol, adrenaline, noradrenaline, T4, T3, and rT3 in healthy males.

Ten days of total energy deprivation evoked the following endocrine changes in 12 healthy, normal-weight males: early and marked reductions and increments in the blood levels of T3 and reverse T3, respectively, with rapid returns to pre-starvation levels after refeeding; a slight and late decrease in the blood levels of T4; a minute reduction of the blood levels of TSH; a pronounced increase in the blood levels of growth hormone, but a return towards pre-exposure levels even before discontinuation of starving; a minor and gradual enhancement of the blood levels of cortisol, and an increase in nocturnal urinary adrenaline excretion. It is assumed that these changes reflect a complex regulatory mechanism, the purpose of which is to secure adequate energy supply to vital organs.

Adult↗
PubMed1977

Bioavailability of propylthiouracil: Interindividual variation and influence of food intake.

The bioavailability of 6-propylthiouracil (PTU) has been examined in eight healthy volunteers, with respect to interindividual variation and influence of food intake. PTU was given as a single oral dose, both in a fasting state and together with a standardized breakfast. Numerous venous blood samples were taken during 5 hours after PTU ingestion, and the concentration of unmetabolized PTU in serum was determined by a specific gas-chromatographic technique. The observations indicate that the amount of PTU absorbed is subject to a large interindividual variation, and that concomitant food intake may exert a minor and non-systematic influence on PTU absorption. Hence, the major issue in PTU therapy is the individualization of the size and interval of dosage. Testing of single-dose PTU kinetics in patients would apparently be helpful.

Administration, Oral↗