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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 55 (1999), S. 1-6 
    ISSN: 1432-1041
    Keywords: Key words Deferiprone ; Iron overloaded patients ; Meta-analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To summarize efficacy and effectiveness in iron overloaded patients treated with the orally active iron chelator deferiprone also known as L1 or, using meta-analysis of the literature. Methods: We reviewed the literature, searching Medline and Embase databases, as well as reviews and other literature on the topic. Inclusion criteria were: original clinical trials reporting results for serum ferritin concentration (SF), hepatic iron concentration or urinary iron excretion (UIE). Efficacy data had to have been reported after ≥3 months of treatment. Data were combined using a random effects model (Cochrane) modified for use with single groups to produce a point estimate and a 95% confidence interval. To summarize the clinical effectiveness, overall proportion of patients where deferiprone was able to reduce serum ferritin was calculated. We also examined average (mg · l−1) serum ferritin levels over the reported time (mean) and absolute decrease from the baseline after therapy. To summarize efficacy, success was defined as the proportion of patients who achieved UIE of 25 mg per day or 0.5 mg · kg−1 · day−1, which equals the average amount received from monthly blood transfusions. We also calculated the overall average level (mg per day) of UIE over the reported time of therapy (mean). As part of a sensitivity analysis, data were analyzed for two ranges of deferiprone dosage: ≤50 mg · kg−1 · day−1 and ≥75 mg · kg−1 · day−1. Results: Of 83 identified references, nine clinical trials met our inclusion criteria, providing data for 129 iron overloaded patients. After a mean of 16 months of therapy (range 6.4–36 months) with 66.4 mg · kg−1 · day−1 (mean) of deferiprone, 75.5% of highly iron overloaded patients had a decrease in serum ferritin from baseline. The average drop in serum ferritin of 0.8 mg · l−1 was 23.5% from baseline. The overall average UIE for therapy was 28.8 mg per day in patients receiving ≥75 mg · kg−1 · day−1 over 8.5 months of therapy. At the same dosage, more than half of the patients (51.8%) achieved negative iron balance. When studies with patients receiving lower dosage (≤50 mg · kg−1 · day−1) were included, the success rate was 45.1%. Conclusion: Overall, deferiprone has clinical efficacy in achieving negative iron balance and reducing body iron burden in highly iron overloaded patients. After an average of 16 months of deferiprone in doses ≥75 mg · kg−1 · day−1, most patients had a decrease in ferritine concentration.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 425-427 
    ISSN: 1432-1041
    Keywords: Methotrexate ; children ; leukaemia ; chronopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is recent evidence that survival is improved when maintenance therapy for acute lymphocytic leukaemia in children is given at night. We have examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In 6 children with leukaemia there was a significant fall in methotrexate plasma clearance at night (from 5.6 to 4.7 ml·kg−1·min−1). Renal clearance of methotrexate tended to fall at night and unbound renal clearance fell significantly (from 17.5 to 8.5 ml·min−1·kg−1 P〈0.05). Creatinine clearance did not exhibit diurnal variation, whereas there was a significant fall in the non-glomerular clearance of methotrexate (from 14.8 to 6 ml·min−1·kg−1). Since methotrexate is a weak organic acid, its tubular secretion depends on urinary pH. At night urinary pH is more acidic, and this may result in more reabsorption and hence reduced renal clearance.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 51-56 
    ISSN: 1432-1041
    Keywords: fentanyl ; cardiac surgery ; fentanyl plasma concentration ; fentanyl sequestration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Immediately following the connection of pediatric patients to cardiopulmonary bypass we have consistently observed a steep decrease in fentanyl plasma concentration (74±8.7%) (mean±SD), much greater than would have been expected from hemodilution alone (50.6%±12.0%) (p〈0.0001). Priming of the pump with 20 ng/ml of fentanyl before connection to the patients did not prevent this phenomenon. In order to study the possibility that fentanyl is sequestered by the bypass, levels of the primed drug in the bypass were assessed before connecting the pump to the children and a steep fall from 20 ng/ml to zero was shown before initiation of bypass. Pharmacokinetic assessment of fentanyl in a closed pump circuit showed that levels of 120 ng/ml fall to 2 ng/ml within 3 min and remain stable at the lower concentration for at least 30 min. Further studies have identified the membrane oxygenator as the major site of fentanyl sequestration. Concentrations across the membrane fall from 120 ng/ml to 10 ng/ml. The attached siliconized tubing is associated with a minor binding effect sufficient to reduce concentrations from 110 to 84 ng/ml. The pvc tubing, aluminium heat exchanger and plastic reservoir had no binding effect on fentanyl. The possibility that a decrease in fentanyl protein binding caused the fall in serum concentration was checked in 5 patients undergoing open heart surgery. After initiation of the cardiopulmonary bypass, there was a significant decrease in albumin serum concentrations from 32.0±2.3 mM to 15.0±1.6 mM (p〈0.0001). Since this decrease is identical to the dilutional effect anticipated on initiation of bypass, it is unlikely that there was any change in free fentanyl concentration from that observed in the prebypass period.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 51-56 
    ISSN: 1432-1041
    Keywords: fentanyl ; cardiac surgery ; fentanyl plasma concentration ; fentanyl sequestration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Immediately following the connection of pediatric patients to cardiopulmonary bypass we have consistently observed a steep decrease in fentanyl plasma concentration (74±8.7%) (mean±SD), much greater than would have been expected from hemodilution alone (50.6%±12.0%) (p〈0.0001). Priming of the pump with 20 ng/ml of fentanyl before connection to the patients did not prevent this phenomenon. In order to study the possibility that fentanyl is sequestered by the bypass, levels of the primed drug in the bypass were assessed before connecting the pump to the children and a steep fall from 20 ng/ml to zero was shown before initiation of bypass. Pharmacokinetic assessment of fentanyl in a closed pump circuit showed that levels of 120 ng/ml fall to 2 ng/ml within 3 min and remain stable at the lower concentration for at least 30 min. Further studies have identified the membrane oxygenator as the major site of fentanyl sequestration. Concentrations across the membrane fall from 120 ng/ml to 10 ng/ml. The attached siliconized tubing is associated with a minor binding effect sufficient to reduce concentrations from 110 to 84 ng/ml. The pvc tubing, aluminium heat exchanger and plastic reservoir had no binding effect on fentanyl. The possibility that a decrease in fentanyl protein binding caused the fall in serum concentration was checked in 5 patients undergoing open heart surgery. After initiation of the cardiopulmonary bypass, there was a significant decrease in albumin serum concentrations from 32.0±2.3 mM to 15.0±1.6 mM (p〈0.0001). Since this decrease is identical to the dilutional effect anticipated on initiation of bypass, it is unlikely that there was any change in free fentanyl concentration from that observed in the prebypass period.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 50 (1996), S. 147-148 
    ISSN: 1432-1041
    Keywords: Key words Felodipine ; Children; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: hypothermia ; fentanyl ; pharmacokinetics ; cardiopulmonary bypass ; hypothermia-induced hypoperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of hypothermia on the disposition of fentanyl was evaluated in 18 children undergoing corrective cardiac surgery. They received a bolus of fentanyl followed by a continuous infusion which was stopped when cardiopulmonary bypass was established and profound hypothermia was achieved (18 °C–25 °C). Fentanyl plasma concentration remained essentially unchanged during hypothermia (6.45 ng/ml 5 min into hypothermia and 5.26 ng/ml 100–140 min later; p〉0.1). In subsequent experiments, the effect of hypothermia on the pharmacokinetics of fentanyl was studied in 4 piglets serving as their own controls. Both distribution volume (Vz) and total body clearance (CL) were significantly smaller during hypothermia. Our studies indicate that being a drug with a large distribution volume and a high hepatic extraction ratio, both CL and Vz are significantly reduced by hypothermia-induced hypoperfusion. In addition, TBC is influenced by the temperature-dependent hepatic metabolism of fentanyl.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 612 (1990), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 197 (1993), S. 932-941 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physica C: Superconductivity and its applications 202 (1992), S. 263-267 
    ISSN: 0921-4534
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physica C: Superconductivity and its applications 230 (1994), S. 340-348 
    ISSN: 0921-4534
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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