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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 19 recordsLinked to original sources
PubMed1979

Influence of food on the absorption of phenytoin in man.

The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.

Adult↗
PubMed1979

Food-induced reduction in bioavailability of atenolol.

The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.

Adult↗
PubMed1979

In vivo absorption of phenytoin from rat small intestine and its inhibition by phlorizin.

In vivo absorption of phenytoin from the small intestine was studied by an in vivo closed segment technique. Phenytoin in concentrations of 1000, 2000, and 4000 mumol/l was administered in dissolved form. Polythylene glycol 4000 was used as a non-absorbable marker. The concentrations of phenytoin in the intestinal lumen, in the mucosa, and in cardiac blood were measured both by spectrophotometry and by gas chromatography. Phenytoin was absorbed very rapidly, and the proportion absorbed increased with increasing dose. Thus, during the first 10 min. about 85 per cent of the largest dose but only 25 per cent of the smallest dose had been absorbed. The phenytoin concentration in mucosa and serum increased in an analogous way; maximum values were observed within the first ten minutes. The concentrations in mucosa and serum were dose dependent during the first ten minutes. 0.01 mmol/l and 1 mmol/l phlorizin significantly reduced the transfer of phenytoin (4000 and 2000 mumol/l) from the gut lumen to the mucosa. No inhibition was observed when the initial phenytoin dose was 1000 mumol/l. The results suggest that an active transport mechanism, sensitive to phlorizin, is involved in the intestinal absorption of phenytoin in the rat.

Animals↗
PubMed1979

Presence and influence of cholinergic nerves in the mouse thyroid.

The presence and influence of cholinergic nerves in the mouse thyroid was studied by histochemistry and measurements of changes in blood radioiodine (BRI) levels. Numerous nerve fibers displaying specific acetyl choline esterase activity were found, not only as a dense network around vessesl but also as single fibers running around and between thyroid follicles. In stress-adapted normal mice, injection of carbamyl choline (CCh) reduced the BRI levels. In mice whose TSH secretion was suppressed by L-T4, neither CCh nor atropine had any measurable influence on the BRI levels when given alone. However, CCh pretreatment reduced and atropine pretreatment enhanced the TSH-induced BRI increase in such animals. It is concluded that the murine thyroid contains numerous cholinergic nerves that may influence not only thyroid blood flow but also thyroid hormone secretion directly. This direct influence appears to be an inhibitory one, mediated via muscarinic receptors in the follicle cells.

Animals↗
PubMed1979

Thyroid and adrenomedullary reactions during sleep deprivation.

The possible influence of a 48 h period of sleep deprivation on the serum concentrations of total and unbound 3,5,3',5'-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), and of total 3,3',5'-triiodothyronine (reverse T3, rT3) was studied in 12 young male volunteers. In addition, plasma concentrations of TSH and the urinary excretion of noradrenaline and adrenaline were examined. Both total S-T4, S-T3 and S-rT3, and unbound S-T4 and S-T3 (unbound rT3 was not calculated) were significantly enhanced following sleep deprivation. P-TSH showed a numerical but statistically not significant increase, while the catecholamines remained unaltered. The results suggest that sleep deprivation provokes enhanced secretion of thyroid hormone(s), supposedly via increased secretion of TSH.

Adrenal Medulla↗
PubMed1979

Active and inactive thyroid hormone levels in elective and acute surgery.

The changes in the plasma or serum concentration of thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5-triiodothyronine (reverse T3, rT3) and cortisol were examined in patients undergoing elective cholecystectomy (n = 10) or acute laparotomy due to peritonitis (n = 11). TSH and T4 showed no essential changes in either group. T3 was reduced already during initiation of anaesthesia and continued to fall during and after surgery in both groups. In the peritonitis group, T3 was reduced already before medical intervention. rT3 displayed changes opposite to those of T3. An increase in cortisol peceded the changes in T3 and rT3 in both groups. T3 and rT3 returned towards normal levels when the patients recovered and resumed oral nutrition. It seems likely that both elective and acute uncomplicated surgery is accompanied by a transient reduction in the extrathyroidal production of the most active hormone, T3, and by a reciprocal increase in the levels of the virtually inactive rT3. The underlying mechanism behind this metabolic adaptation is unclear but may be related to adrenocortical activation and/or to changes in the mode of nutrition.

Aged↗
PubMed1978

Enhancement of dicoumarol bioavailability by concomitant food intake.

The influence of food intake on the bioavailability of dicoumarol from a non-micronized formulation was examined in ten healthy volunteers, by examination of its single-dose kinetics after ingestion of dicoumarol 250 mg with a standardized breakfast and on an empty stomach. Blood samples were collected at regular intervals from 0 to 72 h, and the serum concentration of unmetabolized dicoumarol was determinded by spectrophotometry. Postprandial AUC (area under the curve) values were significantly (p less than 0.01) greater than the preprandial figures, the mean increase being 85 per cent. The results suggest that dicoumarol should always be taken with food.

Adult↗
PubMed1978

Transplacental passage of atenolol in man.

Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.

Adult↗
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↗