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  • 1
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; sulphonylurea ; glibenclamide ; steady state levels ; bioavailability ; food intake ; plasma insulin ; blood glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The steady state concentrations of glibenclamide in serum were measured radioimmunologically in 37 diabetic patients after administration for at least a year. No other antidiabetic drugs had been given. The interindividual variation in glibenclamide concentrations was extremely large (0 to 1520 nmol/l), greatly exceeding the variation in dosage (2.5–25 mg daily). There was no relation between dose and serum concentration of glibenclamide. Only four (9%) patients had fasting blood glucose concentrations below 5.5 mmol/l, and fewer than half had values below 8 mmol/l. In most cases, therefore, the therapy was inadequate. Single-dose kinetics of glibenclamide was assessed in healthy volunteers. Food intake did not influence the bioavailability of a 5 mg dose of glibenclamide. There was no insulin increase in response to glibenclamide unless a meal was also given, and this increase was not significant until 1 h after administration of drug and meal, when the mean serum concentration of glibenclamide had reached 100nmol/l. Even in the fasting state, however, there was a progressive fall in blood glucose after glibenclamide administration, significant within 45 min and with a nadir at 2–2 1/2 h.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 269-274 
    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 403-408 
    ISSN: 1432-1041
    Keywords: glibenclamide ; diabetes ; insulin ; kinetics ; blood glucose ; relationship to meals ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an attempt to assess whether intake of glibenclamide before meals would improve its therapeutic capacity, the present investigation compared the effect of glibenclamide 2.5mg 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 7.5mg. 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 glibenclaimde 2.5mg had been given before the meal than when 2.5 or 7.5mg were given with the meal; a similar, but non-significant tendency was observed after lunch; no consistent difference was seen after dinner. Food intake did not affect glibenclamide kinetics. It appears that administration of glibenclamide 2.5mg before breakfast improved glucose utilization following the breakfast load, due to earlier attainment of an effective concentration of glibenclamide.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 417-419 
    ISSN: 1432-1041
    Keywords: hydralazine ; pregnancy hypertension ; maternal blood level ; neonatal blood level ; transplacental passage ; breast milk level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentrations 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 75ml would not exceed 0.013mg. 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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 233-234 
    ISSN: 1432-1041
    Keywords: acetylator phenotyping ; isoniazid ; dapsone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A comparison was made between the results of acetylator phenotyping by isoniazid (INH) half-life measurements based on 5 samples (0–6 h), and by determination of the ratio of monoacetylated (MAD) to unchanged dapsone (DDS) in a single sample obtained 3 h after dapsone intake. In each of 44 subjects examined, there was unequivocal agreement about classification of the subject as a rapid (INH t1/2 〈2 h; MAD/DDS 〉0.3) or slow (INH t1/2 〉2 h; MAD/DDS 〈0.3) acetylator. It appears that the single-sample (3 h) dapsone test is as reliable as the more laborious and time-consuming INH test for acetylator phenotyping.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 723-725 
    ISSN: 1432-1041
    Keywords: Chlorpropamide ; Type 2 diabetes ; chlorpropamide-alcohol flush test (CPAF) ; skin temperature ; sex effect ; body weight effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Chlorpropamide-alcohol flush (CPAF) tests were carried out in 15 male and 15 female Type 2 diabetics. Twelve subjects were CPAF-positive and 18 were -negative. The two groups did not differ in age or duration of diabetes, but the CPAF-positive subjects weighed less (mean difference 13 kg) and had higher plasma chlorpropamide levels. There was a negative correlation between plasma chlorpropamide and body weight, and a positive correlation between plasma chlorpropamide and the increase in facial skin temperature. Females had higher plasma chlorpropamide, a greater skin temperature increase and lower body weight than males; there were 11 females and only 1 male amongst the 12 CPAF-positive subjects. The findings confirm that plasma chlorpropamide is a major determinant of the CPAF reaction and also show that body weight strongly influences the chlorpropamide level and, consequently, the outcome of the CPAF test. The sex difference in body weight probably accounts for most, if not all, of the sex difference in the incidence of the CPAF.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 95-99 
    ISSN: 1432-1041
    Keywords: glipizide ; Type 2 diabetes ; dosing frequency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two cross-over studies were carried out in 23 patients with Type 2 diabetes, to examine whether glipizide, a potent sulphonylurea with fast and complete absorption and rapid elimination (t1/2〈5 h), can be given once-daily without loss of therapeutic effect. In both studies, patients were randomly assigned to an initial dose of 7.5 mg once daily or 2.5 mg three-times daily, which was increased to 15 mg o.d. or 5 mg t.i.d. if the fasting plasma glucose remained over 10 mmol/l on the lower dosage. In Study 1 (n=11), administration once a day before breakfast was compared with intake before breakfast, lunch and early dinner (5 p.m.) and in Study 2 (n=12) the comparison was between intake once-daily before breakfast and dosing before breakfast, lunch, and at bedtime (10 p.m.). Neither the 24-hour urinary glucose excretion nor HbA1, fasting plasma glucose, insulin or C-peptide levels differed between the once and three times daily administration with the third dose given before early dinner. The nadir plasma levels of glipizide were not significantly different and were often too low to be detected. Postponing the third dose until 10 p.m. did not produce any improvement in HbA1 or in fasting plasma glucose, insulin or C-peptide. The mean nadir glipizide levels following this schedule were twice as high as those after once-daily administration. As expected, the plasma glipizide after breakfast was higher when the whole dose was taken before breakfast than when it was divided. The corresponding plasma level of insulin was higher and that of plasma glucose was lower. The after-lunch levels of glipizide did not differ significantly, and there was no after-lunch difference in plasma insulin or glucose. It appears that the major effect of glipizide is to augment insulin availability following meals, whilst it has little influence on nocturnal glucose control. In a daily dose of 7.5 mg or more, glipizide can be taken once daily without loss of efficacy, at least in areas with Northern European meal schedules.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: indomethacin ; diflunisal ; pharmacokinetics ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The single-dose pharmacokinetics of indomethacin following 100 mg rectally was measured in two groups of 8 healthy subjects before and after diflunisal 500 mg p.o. once daily, or 500 mg in the morning and 1000 mg in the evening, until steady state conditions were reached. A further group of 8 healthy subjects was given 50 mg indomethacin rectally before and after diflunisal 500 mg p.o. twice daily. High dose diflunisal (1500 mg/day) decreased the renal clearance of indomethacin from 21.9 to 1.8 ml/min (92%) and reduced the renal excretion of both unchanged (63%) and conjugated (82%) indomethacin. The apparent total body clearance (0.12 l/h/kg), apparent volume of distribution (0.98 l/kg), and volume of distribution at steady state (0.80 l/kg) were decreased by 47%, 35% and 30%. The maximum plasma concentration (2.4 µg/ml) and total area under the curve (13.0 µg × h/ml) were increased by 40% and 119%, respectively. The terminal elimination half-life (5.7 h) and mean residence time (6.7 h) were slightly prolonged (7.0 h and 8.8 h) in the presence of diflunisal. The contribution of metabolism to the overall elimination of indomethacin was increased by only 2%. Similar results were obtained when the subjects were challenged with the low dose of diflunisal (500 mg/day), although the magnitude of the changes were smaller. The interaction between indomethacin and diflunisal may be due to competition both at the metabolic (conjugation) and the excretory (tubular secretion) levels. When the subjects were given 50 mg indomethacin and diflunisal 1000 mg/day simultaneously, the achieved maximum plasma concentration of indomethacin (2.53 µg/ml) was comparable to that seen after 100 mg in the absence of diflunisal (3.1 µg/ml), but the AUC was greater (21.7 µg × h/ml vs 13.0 µg × h/ml). Adverse central nervous reactions were more frequent and more pronounced at higher plasma indomethacin concentrations.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1041
    Keywords: Glipizide ; Insulin secretion ; Diabetes mellitus ; NIDDM ; sulphonylurea treatment ; hypocaloric diet weight control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached ≤6.0 mmol·l−1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of −2.8 kg by dietary control, did achieve a fasting blood glucose ≤6.0 mmol·l−1 after addition of ≤20 mg glipizide daily. They had a sustained (≥2 years) increase in meal-induced insulin secretion (32% increase in postprandial C-peptide AUC), and a sustained reduction in postprandial hyperglycaemia (34% reduction in AUC). Ten of the patients took a mean daily dose 〈5mg (4.8 mg) and had a sustained increase in insulin secretion rate (increased C-peptide slope). The 15 patients had no elevation of basal insulin secretion and no impairment of weight reduction. The remaining 8 subjects, who showed little or no weight reduction on dietary control, had little or no reduction in fasting blood glucose despite long-term treatment with 20 mg glipizide daily, a less sustained increase in meal-induced insulin secretion, a smaller reduction of postprandial hyperglycaemia, and an increase in body weight. On diagnosis the 8 subjects did not differ from the other 15 subjects in age, body weight, blood glucose, HbA1c, C-peptide or insulin, nor in their glucose and insulin responses to a test dose of glipizide; the main reason for the apparent drug failure appeared to be deficient compliance with dietary regulation rather than a primary inability to respond to sulphonylurea treatment. The findings indicate that glipizide is able to promote and maintain increased meal-induced insulin secretion and near-normal fasting and non-fasting blood glucose levels without continuous B cell stimulation. However, these improvements prevail mainly in subjects who persist with hypocaloric dietary regulation.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1041
    Keywords: glibenclamide ; glipizide ; pharmacokinetics ; metabolic effects ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen Type 2 diabetics were treated for 4-week periods with once daily (10 mg) glibenclamide, glipizide and placebo according to a double-blind cross-over protocol. Post-dose glipizide concentrations were three times higher than those of glibenclamide, due to the incomplete bioavailability of the latter. On the other hand, pre-dose drug levels were similar, as an expression of the slower absorption and/or elimination of glibenclamide. Both active treatments reduced postprandial blood glucose concentrations and 24-hour urinary glucose excretion to a similar degree, but fasting blood glucose concentrations were slightly lower during glibenclamide treatment. Both active treatments enhanced fasting and postprandial insulin and C-peptide concentrations, the C-peptide response being greater after glipizide than after glibenclamide. Plasma glucagon and GIP concentrations were not significantly affected. Insulin sensitivity was increased by glibenclamide but not by glipizide. Neither therapy affected insulin binding to erythrocytes. It appears that both glibenclamide and glipizide improved glucose metabolism by sustained stimulation of insulin secretion, which was most pronounced with glipizide. Only glibenclamide improved insulin sensitivity and was slightly more active than glipizide on fasting blood glucose levels. The differences may be consequences of the pharmacokinetics, but differences in pharmacodynamics cannot be excluded.
    Type of Medium: Electronic Resource
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