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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 6 (1973), S. 256-260 
    ISSN: 1432-1041
    Keywords: K 4277 ; anti-inflammatory agents ; metabolism ; man ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The fate of the new analgesic and anti-inflammatory agent α-[4-(1-oxo-2-iso-indolinyl)-phenyl]-propionic acid (compound K 4277) in healthy volunteers has been investigated by a radio-isotope method and gas-liquid chromatography. After oral administration, the drug was absorbed rapidly and completely and occurred in plasma mainly as unchanged compound bound extensively to plasma proteins. Its disappearance from plasma followed at least a bi-exponential function and was almost complete in 24 to 48 h. Most of the drug is excreted in urine as a glucuronide and a lesser amount as the unchanged compound. There were only negligible amounts of other metabolites.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 4 (1971), S. 12-17 
    ISSN: 1432-1041
    Keywords: Beta-blockers ; tilting ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Inhibition of heart rate increase during passive tilting was used as a test for rapid screening of two new benzo-bicyclic beta-blocking agents in man. Eight healthy volunteers were treated with single oral doses of the new drugs (K 4423, K 4540) and two oral doses of propranolol as reference drug. The test provided a useful means of assessing the relative potencies of these new drugs in man. The study showed that beta-blockers, in doses large enough substantially to inhibit the increase in heart rate during passive tilting, may decrease systolic and to a lesser extent diastolic blood pressure in normotensive subjects.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: fenoldopam ; digoxin ; drug interaction ; CHF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The potential interaction between fenoldopam, a DA1 selective agonist, and digoxin has been studied in 10 patients with heart failure (NYHA Class II or III) on chronic digoxin treatment. Plasma levels and urinary recovery of the glycoside were monitored for 24 h before and after 9 days of treatment with fenoldopam 100 mg tid. Fenoldopam caused a small, non-significant decrease in the mean steady state plasma concentration and area under the plasma concentration curve of digoxin. As the clearance of digoxin was unchanged there does not appear to be an interaction between fenoldopam and digoxin at the level of the renal tubule.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; food effect on bioavailability ; repeated administration ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on bioavailability of indobufen tablets was investigated in 6 healthy volunteers. Subsequently, the same subjects took 100 mg b.i.d. for 7 days. Plasma levels and urinary excretion of indobufen were determined by GLC. Platelet aggregation induced by several concentrations of adrenaline was determined turbidimetrically at various times after the first and last doses. The absorption of indobufen tablets was not substantially impaired by the presence of food in the GI tract, although peak plasma levels and AUCs were slightly reduced after food. Pharmacokinetic analysis of plasma and urinary levels of indobufen did not indicate any change in drug disposition after repeated dosing. Adrenaline-induced platelet aggregation was markedly inhibited for up to 12 h after the first dose and the intensity and duration of this effect did not change after repeated administration. A twice-daily dosing appears suitable for clinical trials.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 12 (1977), S. 383-386 
    ISSN: 1432-1041
    Keywords: Benzodiazepine ; temazepam ; pharmacokinetics ; bioavailability ; hard and soft gelatine capsules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 1 (1969), S. 123-130 
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-six Swiss physicians took part in a study in which the effects of an orally administered new beta-receptor blocking agent, Trasicor®, were assessed in out-patients with disturbances of cardiac rhythm. Ninety-eight patients were treated for 3 weeks with daily doses ranging from 20 to 120 mg, the most commonly employed daily dose being 60 mg. The patients were examined before treatment and again after 1, 3, 7, 14 and 21 days of treatment. The compound proved highly effective in decreasing heart rate in sinus tachycardia and ventricular rate in chronic auricular fibrillation, both at rest and during effort. Trasicor also abolished, or substantially reduced, the frequency of attacks of paroxysmal supraventricular tachycardia and ventricular ectopic beats. — In hypertensive patients, Trasicor elicited a statistically significant decrease in both the systolic and diastolic blood pressures, whereas in normotensives only the systolic blood pressure was affected to a statistically significant extent. - Side effects were usually mild and transient; treatment had to be withdrawn in only a small percentage of patients.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7241
    Keywords: ibopamine ; congestive heart failure ; diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical efficacy and safety of ibopamine and diuretic therapy were compared in a multicenter, multinational, parallel, positive-controlled, randomized, double-blind, 12-week study, involving 103 patients with mild CHF (NYHA Class II). Body weight, NYHA functional class, symptom assessment scores, laboratory blood tests, and exercise testing were evaluated at baseline at interim visits and at the end of 12 weeks. Clinical events were monitored throughout the study. There was no difference in any of the considered parameters between the two patient groups at baseline and at the end of the 12-week evaluation. A trend of improvement in clinical conditions that did not reach statistical significance was noted in each group throughout the study, as a probably „trial effect.” Five patients on ibopamine had severe clinical events leading to drug discontinuation (CHF worsening, ventricular tachycardia, elevation of liver transaminases, headache, gastrointestinal disorders) and five on diuretic therapy experienced serious side effects (skin rash, palpitation, atrial fibrillation, elevation of liver transaminases, manic episode). One patient died while on diuretic therapy. Only headache and skin rash were considered to be related to the therapy (ibopamine and diuretic therapy, respectively). Our trial suggests that ibopamine can be safely and effectively used as an alternative for diuretics for up to 3 months in patients with mild CHF.
    Type of Medium: Electronic Resource
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