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  • 1
    Electronic Resource
    Electronic Resource
    Effects of fenflumizole on aggregation ex vivo of human platelets and formation of thromboxane B2 and 6-keto-prostaglandin- $$F_{1\alpha } $$ (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 711-717 
    Details
    ISSN: 1432-1041
    Keywords: fenflumizole ; thromboxane formation ; prostacylin formation ; platelet aggregation ; arachidonic acid ; healthy subjects ; blood clotting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl)imidazole), a new non-steroidal anti-inflammatory drug, was given to healthy subjects in single oral doses of 0.1, 1 and 2 mg/kg. The effect of the drug was followed for up to 8 h by repeated tests of arachidonic acid-induced platelet aggregation and was related to its concomitant plasma concentration. Fenflumizole reversibly inhibited platelet aggregation and the degree of inhibition was found to be linearly correlated with the log plasma concentration. There was depression of the formation of thromboxane B2 and 6-keto-prostaglandin F1α (the stable metabolites of thromboxane A2 and prostacyclin) in clotted whole blood measured by radioimmunoassay after fenflumizole 1 mg/kg. This effect was directly related to the concentration of the drug in plasma, the maximum effect being reached at fenflumizole concentrations 〉200 ng/ml. EC50-values for inhibition of the formation of thromboxane B2 and 6-keto-prostaglandin $$F_{1\alpha } $$ were approximately 20 and 40 ng/ml, respectively. The results suggest that orally administered fenflumizole is a potent inhibitor of platelet aggregation and prostanoid formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541930
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  • 2
    Electronic Resource
    Electronic Resource
    Arachidonic acid — Induced platelet aggregation and prostanoid formation in whole blood in relation to plasma concentration of indomethacin (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 163-169 
    Details
    ISSN: 1432-1041
    Keywords: indomethacin ; platelet aggregation ; prostanoids ; plasma concentration ; arachidonic acid ; thromboxane B2 ; 6-keto-prostaglandin F1α ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single oral dose of indomethacin 1 mg/kg was given to 6 male and 6 female volunteers. The formation of thromboxane B2 (TXB2) and 6-ketoprostaglandin F1α (6-keto-PGF1α) in clotting whole blood was measured by radioimmunoassay, and platelet aggregation induced by archidonic acid (AA) was measured with a plasma aggregometer. The results were related to the concomitant plasma concentration of indomethacin. The maximum plasma concentration ranged between 3.24 and 8.11 µg/ml and the elimination half-life between 4 and 11 h. Formation of the prostanoids was reversibly inhibited, with maximum suppression when the drug concentration in plasma exceeded 0.5–1.0 µg/ml; the IC50 was approximately 0.1 µg/ml. Platelet aggregation was also reversibly inhibited. The correlation between the formation of prostanoids and the different phases of the aggregatory response to exogenous AA is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609686
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of nimodipine in patients with aneurysmal subarachnoid haemorrhage (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 421-425 
    Details
    ISSN: 1432-1041
    Keywords: nimodipine ; subarachnoid haemorrhage ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 µg/kg/min) for at least 7 days, and then orally (45 mg × 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6±1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.77 l/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range〈3–38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0–96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607954
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of cloxacillin in patients undergoing hip or knee replacement (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 407-411 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cloxacillin ; Hip replacement ; Knee replacement; pharmacokinetics ; sex differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of cloxacillin was investigated in 14 men and 24 women undergoing cemented hip (n = 19; age range 56–90) or knee replacement surgery (n = 19; age range 51–84) for osteoarthritis. Cloxacillin 1 g was given intravenously as a bolus dose at the induction of anesthesia, and plasma samples and urine were collected for 6 h. Drug levels were determined using HPLC. Results: Preoperative serum creatinine levels were 84 μmol · l−1 in hip patients and 72 μmol · l−1 in knee patients. The calculated values for creatinine clearance were 63 and 85 ml · min−1 · 1.73 m−2, respectively. Total clearance of cloxacillin was 134 ml · min−1 · 1.73 m−2 in eighteen evaluated patients undergoing hip replacement, and 162 ml · min−1 · 1.73 m−2 in eighteen patients undergoing knee surgery. Renal clearance was 72 and 79 ml · min−1 · 1.73 m−2, respectively. Non-renal clearance was 57 ml · min−1 · 1.73 m−2 in hip patients and 77 ml · min−1 · 1.73 m−2 in knee patients. Renal clearance of cloxacillin correlated with the estimated creatinine clearance (r = 0.652). Although women received higher doses than men (median 2.02 vs 2.32 mmol · 1.73 m−2), there were no sex differences in clearance corrected for body surface area. Conclusion: Total clearance of cloxacillin was lower in patients undergoing hip replacement than in patients undergoing replacement of the knee, but there was no difference between men and women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050310
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    Paper (German National Licenses)
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