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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 145 records · Page 8Linked to original sources
PubMed1983

Influence of food intake on the bioavailability of zimeldine and its active metabolite, norzimeldine.

The possible influence of concomitant food intake on the bioavailability of the novel antidepressant zimeldine and its active metabolite norzimeldine was assessed in ten healthy female volunteers, who ingested a single dose of 200 mg zimeldine on an empty stomach and together with a standardized breakfast of 1 840 kJ. The plasma concentrations of zimeldine and norzimeldine were measured by a selective modern liquid chromatographic technique. Neither the peak concentration nor time to reach peak concentration nor elimination half-life nor the total area under the curve (AUC) of zimeldine was affected by concomitant food intake. For norzimeldine, the peak concentration showed a 10% reduction, but there was no change in any other parameter. Thus, the bioavailability of zimeldine and of its active metabolite norzimeldine is unaffected by food intake, suggesting that the drug need not be taken in a strictly defined relation to meals.

Adult↗
PubMed1983

Pharmacokinetics and effects of glibenclamide in two formulations, HB 419 and HB 420, in type 2 diabetes.

The pharmacokinetics and effects of glibenclamide in two formulations, the established formulation, HB 419 (5 mg) and the new micronized formulation, HB 420 (3.5 mg) were compared after once daily administration of each to eight type 2 diabetics in a double blind crossover trial. On the second day of administration of each formulation, blood glucose and serum C-peptide, insulin and glibenclamide concentrations (radioimmunoassays) were measured for eight hours after tablet ingestion. Although the amount of glibenclamide per tablet of HB 420 was lower than the amount of glibenclamide per tablet of HB 419, serum concentrations of drug were higher after HB 420 than after HB 419, and were also less variable between individuals. However, there were no corresponding differences in serum C-peptide and insulin levels, or in blood glucose levels. Thus intestinal absorption of glibenclamide appeared to be greater and less variable from HB 420 than from HB 419 but both formulations apparently produced drug concentrations in the serum well above that needed for maximum therapeutic response in the patients studied.

Aged↗
PubMed1983

Opposite effects of carbohydrate and protein on phenytoin absorption in man.

Food intake has been found to enhance the absorption of phenytoin, as judged from single-dose studies in healthy volunteers taking phenytoin (acid) with and without a standardized breakfast of 1,840 kJ. In order to investigate whether this effect was due to food intake as such or to the ingestion of a certain nutrient, the influence of carbohydrate, fat, and protein, respectively, on phenytoin (acid) absorption was examined in ten healthy volunteers. The nutrients were given separately in amounts corresponding to those of the standardized breakfast previously employed. Phenytoin concentrations in plasma were measured by high-pressure liquid chromatography. The results indicate that, while fat had no measurable influence, carbohydrate may enhance, and protein reduce, the absorption of phenytoin.

Adult↗
PubMed1983

Influence of food intake on antihypertensive drugs: spironolactone.

A series of studies has been initiated to examine the influence of concomitant food intake on the effects of antihypertensive drugs during long-term therapy. In the present study, the therapeutic effect of spironolactone and the steady-state concentrations of its major, active metabolite canrenone were compared in 10 hypertensive patients after two 60-day periods of spironolactone treatment, 100 mg once daily, prescribed to be ingested before and together with breakfast, respectively. There was no significant difference in the blood pressure and heart rate values during the two treatment periods, and the canrenone levels were similar. As spironolactone can cause gastric irritation, the present findings support the recommendation that spironolactone always be prescribed for once-daily intake together with breakfast.

Adult↗
PubMed1983

Clinical pharmacokinetics of sulfonylureas: a brief review.

All sulfonylureas seem to have similar mechanisms of action. Nevertheless, they may differ in their clinical effects because of differences in their pharmacokinetics and intrinsic activities. Second generation sulfonylureas, such as glibenclamide and glipizide, are much more potent than first generation sulfonylureas, such as tolbutamide and chlorpropamide. The former are, in fact, active at concentrations of the order of nmol/l, while the latter are active in the range of mumol/l. Accordingly, glibenclamide and glipizide are more efficient, and probably also less prone to cause pharmacokinetic interactions with other drugs, and with ethanol. In addition, glipizide and glibenclamide (new formulations) are completely bioavailable, which is a further advantage. Glipizide has a more rapid absorption and onset of action as well as a shorter half-life and duration of effect than glibenclamide. Accordingly, glibenclamide has a better effect on nocturnal and fasting blood glucose levels, but its use may also involve a greater risk of long-lasting hypoglycemia. At daily dosages of 5 mg or more, divided dosage seems unnecessary with glipizide, since effective concentrations will prevail throughout most of a 24 hour period. Efficacy may be improved if either drug is administered before, rather than together with, breakfast. High doses of glipizide may impair, rather than improve, glucose balance.

Biological Availability↗
PubMed1982

Influence of hyperthyroidism on the kinetics of methimazole, propranolol, metoprolol and atenolol.

The kinetic profiles of oral methimazole 40 mg, propranolol 80 mg, metoprolol 100 mg and atenolol 100 mg were compared in hyperthyroid patients both during the hyper- and euthyroid states. for methimazole, neither the peak concentration (Cmax), the time to reach peak concentration (tmax), the elimination half-life (t 1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p less than 0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t 1/2's were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.

Administration, Oral↗
PubMed1982

Improved effect of glibenclamide on administration before breakfast.

In an attempt to assess whether intake of glibenclamide before meals would improve its therapeutic capacity, the present investigation compared the effect of glibenclamide 2.5 mg t.i.d. given before and together with meals. In addition, these effects were compared with that of glibenclamide given as a single morning dose of 7.5 mg. The subjects studied were six Type 2 diabetics not previously exposed to sulphonylurea drugs. Irrespective of dosage and mode of administration, addition of glibenclamide to a standardized breakfast, lunch and dinner enhanced plasma IRI concentrations and reduced blood glucose concentrations as compared to administration of meals without the drug. The different modes of glibenclamide administration did not differ significantly with respect to IRI responses. However the blood glucose reduction after breakfast was significantly greater when glibenclamide 2.5 mg had been given before the meal than when 2.5 or 7.5 mg were given with the meal; a similar, but non-significant tendency was observed after lung; no consistent difference was seen after dinner. Food intake did not affect glibenclamide kinetics. It appears that administration of glibenclamide 2.5 mg before breakfast improved glucose utilization following the breakfast load, due to earlier attainment of an effective concentration of glibenclamide.

Adult↗
PubMed1982

Transplacental passage and breast milk concentrations of hydralazine.

The concentration of "real" and "apparent" (= "real" hydralazine + acid-labile hydrazones) hydralazine in maternal and umbilical plasma obtained at delivery of 6 women treated with hydralazine and atenolol for pregnancy hypertension were measured by gas chromatography. In one of the patients, the concentrations of the same substances were subsequently measured in breast milk. "Apparent" hydralazine reached higher levels in umbilical than in maternal blood. The concentration of "real" hydralazine seemed to be at least as high in the fetus as in the mother. On the other hand, even though the fraction of "real" (i.e. presumably active) hydralazine was greater in milk than in plasma, the total concentration was smaller, and the estimated dose per milk feed of 75 ml would not exceed 0.013 mg. Thus, hydralazine treatment of the pregnant woman would expose her fetus to effective concentrations of the drug, but breast feeding would not result in a clinically relevant concentration in the infant.

Adult↗
PubMed1982

Bioavailability of acetylsalicylic acid and salicylic acid from rapid-and slow-release formulations, and in combination with dipyridamol.

Acetylsalicylic acid (ASA) is a strong, irreversible inhibitor of platelet aggregation, but loses this activity following first-pass deacetylation to salicylic acid (SA). In order to compare the bioavailability of unchanged ASA from rapid- and slow-release formulations, the single-dose concentration profiles of ASA and SA were studied in healthy volunteers following intake of two different rapid-release (conventional and effervescent tablets) and three different slow-release (microencapsulated ASA in tablets and in capsules, and enteric-coated tablets) formulations of ASA, and of one slow-release formulation of sodium salicylate. Since anti-platelet therapy with ASA is often combined with dipyridamol, the influence of this drug was also examined. The concentrations of ASA and SA were measured by high-pressure liquid chromatography. While the bioavailability of SA from the 5 ASA formulations was essentially equal and similar to that of the salicylate formulation, the bioavailability and peak concentrations of ASA appeared to be the much greater after rapid-release than after slow-release formulations. Indeed, ASA was only rarely detected in systemic blood following intake of slow-release ASA. Co-administered dipyridamol did not significantly influence the kinetics of ASA or SA. It appears that rapid-release formulations of ASA should be prefered in anti-platelet therapy, either alone or in combination with dipyridamol.

Adult↗
PubMed1982

Impaired effect of sulfonylurea following increased dosage.

Ten Type 2 diabetics were examined during long-term treatment, at two dosage levels, with chlorpropamide once daily and glipizide t.i.d. Drug concentrations were measured by gas chromatography and high-pressure liquid chromatography, respectively, plasma insulin (IRI) by radio-immunoassay, and blood glucose enzymatically. Both drugs gave continuous sulfonylurea exposure, even at the lower dosage, and the mean plasma concentrations were almost doubled after the increase in dose. Neither the IRI nor the glucose response to meals showed any therapeutic improvement following the increase in chlorpropamide dosage. The lower dosage of glipizide produced better glucose utilization than chlorpropamide. On the other hand, the increased dose of glipizide led to impairment instead of further improvement. As this was associated with enhanced rather than reduced IRI levels, the impairment might have been due to increased peripheral insulin resistance. Thus, glipizide offers a therapeutic advantage over chlorpropamide, but its effectiveness may be restricted not only by limitations set by the disease, but also by counter-regulatory mechanisms that develop during continuous exposure to sulfonylureas at high levels.

Aged↗
PubMed1982

Influence of sulfonylureas on the secretion, disposal and effect of insulin.

The influence of sulfonylurea on the secretion, disposal and effect of insulin was studied in 9 Type 2 diabetics during 3 one-month courses of treatment with a) chlorpropamide (t1/2 greater than 24 h) once daily, b) glipizide (t1/2 = 2-4 h) once daily, and c) glipizide in divided doses. Food intake by each patient was identical during each period. Blood concentrations of immunoreactive insulin (IRI) and C-peptide (radioimmunoassays), and of glucose (enzymatic assay), chlorpropamide (gas chromatography) and glipizide (high-pressure liquid chromatography) were determined before and after breakfast and lunch on the 4th day of each examination period. All comparisons were intraindividual. Despite the lunch-time dose of glipizide given during the divided dose treatment, once-daily administration of this drug led to higher drug concentrations not only after breakfast but also for the first few hours after lunch. Divided dosage, on the other hand, led to higher concentrations later. In contrast to once-daily dosage, continuous exposure to glipizide was found in most patients. Chlorpropamide gave the most continuous sulfonylurea exposure. The blood glucose levels were inversely related to the concurrent sulfonylurea concentrations; glucose levels after breakfast and lunch were lowest during once-daily glipizide, whereas the fasting level was lowest during chlorpropamide treatment. The IRI response to breakfast was 60%-70% higher during once-daily glipizide than during the other two treatments but the C-peptide responses to breakfast were almost identical. Thus, the greater after-breakfast availability of peripheral insulin appeared to be due to an effect of glipizide on the extrapancreatic disposal of the hormone.

Aged↗
PubMed1982

Therapeutic equivalence of sulfaisodimidine 2 g twice daily and 1 g four times daily in lower urinary tract infections.

The serum concentrations and clinical effects of sulfaisodimidine given during 12 days were examined in two groups of patients with uncomplicated lower urinary tract infection. Group I (n=12) received the drug in a conventional dosage, 1 g four times daily, and group II (n=14) in a dose of 2 g twice daily. The serum concentrations of sulfonamide at steady state (day 7) and one day after cessation of therapy (day 13) did not differ significantly between the groups. With the exception of one patient in group I, both subjective and objective symptoms vanished during treatment and remained absent for at least 4 weeks thereafter. Two patients in each group developed signs of sulfonamide allergy. Thus, the two regimens seemed to be equally efficient, and the risk of therapy failure due to low blood concentrations of sulfaisodimidine should not be greater when the drug is given in a dosage of 2 g twice daily than when it is administered in the conventional way. Hence, the latter, simpler regimen can be recommended.

Adult↗
PubMed1982

Influence of beta-adrenoceptor blocking agents on lymphocyte function in vitro.

1 In order to assess whether beta-adrenoceptor blocking agents may have an immunomodulatory influence, the in vitro effect of propranolol metoprolol and atenolol on mitogenic activation of human peripheral blood lymphocytes was studied. To investigate further the mechanism of this influence, the effects of quinidine and two other membrane stabilizing agents were examined. 2 At 100 and 1000 mumol/l, both (+)-propranolol, (-)-propranolol and (+/-)-propranolol evoked a strong reduction of mitogenic lymphocyte activation. A similar effect was obtained with quinidine. Even at 1000 mumol/l metoprolol, had only a slight suppressive effect and atenolol had no suppressive influence at all. 3 It appears that propranolol may suppress mitogenic activation of lymphocytes, and that the effect may be ascribed to membrane stabilization rather than to beta-adrenoceptor blockade.

Adrenergic beta-Antagonists↗
PubMed1982

Alteration of thyroid hormone economy during alcohol withdrawal in alcoholics.

Alcohol and alcohol withdrawal may affect nutritional status in many different ways, including effects on thyroid activity. The influence of alcohol withdrawal on thyroid hormone economy was investigated by measurements of changes in the serum concentrations of thyroxine (T4), 3, 5, 3'-triiodothyronine (T3), 3, 5, 5'-triiodothyronine (reverse T3, rT3), and thyrotropin (TSH) in chronic alcoholics experiencing different degrees of alcohol abstinence. In addition, the serum concentrations of ethanol were measured at entrance. There was no significant correlation between the entrance serum ethanol levels, on the one hand, and those of T4, T3, rT3, or TSH, on the other. However, during severe ethanol abstinence (with or without delirium tremens), there was a significant increase in the serum levels of T4 and rT3, but not in those of T3 and TSH. These findings indicate that (severe) alcohol abstinence can interfere with thyroid hormone economy, either by enhancing thyroid hormone secretion or by reducing T4 and rT3 deiodination. It is an open question whether this represents a beneficial adaptation to the metabolic disturbance caused by alcohol intoxication and abstinence, or an additional derangement that warrants nutritional or other therapeutic measures.

Alcohol Withdrawal Delirium↗
PubMed1982

Influence of food on the bioavailability of "real" and "apparent" hydralazine from conventional and slow-release preparations.

The influence of concomitant food intake on the bioavailability of hydralazine was studied in healthy volunteers following single-dose administrations in the fasting state and together with a standardized breakfast meal of 1840 kJ (440 kcal). Both "real" (presumably active) and "apparent" (= total = "real" hydralazine + acid-labile hydrazones formed after hydralazine ingestion) hydralazine were determined by gas chromatography. Concomitant food intake seemed to enhance the bioavailability of both "apparent" and "real" hydralazine following ingestion of conventional hydralazine tablets. On the other hand, food intake did not significantly affect hydralazine bioavailability from a slow-release preparation. The enhanced effect of food on hydralazine bioavailability from the conventional preparation is probably due to reduced first-pass metabolism.

Acetylation↗
PubMed1982

Influence of food and of age on nitrazepam kinetics.

The influence of food intake and of age on the kinetics of nitrazepam was examined in eight young and eight elderly healthy volunteers after single-dose administration of the drug. Serial blood samples were obtained during 0-24 hr, and the serum concentrations of nitrazepam were determined by gas chromatography. Concomitant food intake had no apparent influence on the absorption rate or on the bioavailability of nitrazepam in the young subjects, and there was no significant difference in nitrazepam kinetics between young and elderly subjects. Accordingly, nitrazepam may be taken together with food as well as on an empty stomach, at least in young subjects, and the increased nitrazepam sensitivity often seen in elderly subjects does not seem secondary to age-dependent pharmacokinetic differences.

Adult↗