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  • 1
    Electronic Resource
    Electronic Resource
    Methotrexate in juvenile rheumatoid arthritis (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 507-511 
    Details
    ISSN: 1432-1041
    Keywords: Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5–16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg·kg−1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193703
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Controlled trial of methotrexate in patients with severe chronic asthma (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 347-349 
    Details
    ISSN: 1432-1041
    Keywords: Asthma ; Methotexate ; steroid-sparing effect ; blood levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The aim of this study was to investigate the efficacy and adverse effects of methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with severe asthma requiring continuous treatment with oral steroids at the Outpatient Department of Helsinki University Central Hospital. The study was a randomised, double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of oral steroids administered was 10.9 (3.2–28) mg · day−1, and the mean dose of inhaled steroids administered was 2.3 (1.6–3.2) mg budesonide or beclomethasone. The average dose of oral steroids administered was 12.8 mg · day−1 during the last 2 placebo weeks but only 7.9 mg · day−1 during the last 2 weeks with MTX treatment. The reduction in daily dose of oral steroids was 38%, while daily bronchodilator use was reduced by 22%. During MTX treatment the patients experienced significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients reported better asthma control during MTX treatment. The peak expiratory flow rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX and placebo treatments. There was no statistical correlation between serum MTX concentration and clinical improvement. No serious adverse effects of MTX were found during the study. It was concluded that low-dose MTX may be beneficial for severe chronic asthma and that this therapy is well tolerated by patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00203775
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    On the bioavailability of 2-chloro-2′-deoxyadenosine (CdA) (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 579-582 
    Details
    ISSN: 1432-1041
    Keywords: 2-Chloro-2′-deoxyadenosine (CdA) ; omeprazole ; food ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral CdA (0.24 mg/kg) was studied in 4 patients (1 with hairy cell leukaemia and 3 with B-cell chronic lymphocytic leukaemia) to determine any effect of food and fasting with and without omeprazole. Food intake did not significantly influence the bioavailability of CdA (42% after food intake vs 46% while fasting) but it did reduce the maximum plasma concentration (Cmax) by 40%; 83 compared to 116 nM while fasting. The time to reach maximum concentration (tmax) was delayed about 0.8 h after food intake. Pretreatment with omeprazole did not significantly influence the bioavailability of CdA (51% vs 46% without), or the interindividual variability in bioavailability in the fasting state (C.V. 0.26 with and C.V. 0.27 without). In conclusion, there was a small, though not statistically significant reduction in the bioavailability of CdA after food intake. Omeprazole did not significantly improve the bioavailability of CdA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02440863
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Protein binding of 2-chloro 2′-deoxyadenosine (cladribine) in healthy subjects and in patients with leukaemia (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 563-564 
    Details
    ISSN: 1432-1041
    Keywords: 2-Chloro-2′-deoxyadenosine (CdA) ; Protein binding ; Cladribine ; pharmacokinetics ; leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The plasma protein binding of 2-chloro-2′-deoxyadenosine (CdA) at 37°;C was studied by ultrafiltration in 5 healthy volunteers, in 11 patients with haematological malignancies and in purified protein preparations. In the patients, the binding of CdA to plasma proteins was 25.0% and in healthy subjects it was 21.1%. In a solution of human serum albumin (40 g·1−1), 24.3% CdA was bound, but less than 5% was bound in a solution of α1-acid-glycoprotein (0.7 g·1−1). No dependence of binding on the concentration of CdA was found within a range 25–1000 nmol·1−1. In conclusion, due to its limited binding to plasma proteins, any change in the binding of CdA is unlikely to have a major influence on its pharmacological effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196117
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Controlled trial of methotrexate in patients with severe chronic asthma (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 347-349 
    Details
    ISSN: 1432-1041
    Keywords: Key words Asthma ; Methotrexate; steroid-sparing effect ; blood levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The aim of this study was to investigate the efficacy and adverse effects of methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with severe asthma requiring continuous treatment with oral steroids at the Outpatient Department of Helsinki University Central Hospital. The study was a randomised, double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of oral steroids administered was 10.9 (3.2–28) mg ⋅ day−1, and the mean dose of inhaled steroids administered was 2.3 (1.6–3.2) mg budesonide or beclomethasone. The average dose of oral steroids administered was 12.8 mg ⋅ day−1 during the last 2 placebo weeks but only 7.9 mg ⋅ day−1 during the last 2 weeks with MTX treatment. The reduction in daily dose of oral steroids was 38%, while daily bronchodilator use was reduced by 22%. During MTX treatment the patients experienced significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients reported better asthma control during MTX treatment. The peak expiratory flow rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX and placebo treatments. There was no statistical correlation between serum MTX concentration and clinical improvement. No serious adverse effects of MTX were found during the study. It was concluded that low-dose MTX may be beneficial for severe chronic asthma and that this therapy is well tolerated by patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050029
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Hydrophobicity parameters of 2-chloro-2'-deoxyadenosine and some related analogues and retention in reversed-phase liquid chromatography
    Amsterdam : Elsevier
    Journal of Chromatography A 667 (1994), S. 37-45 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0021-9673(94)89049-8
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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