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  • 1
    ISSN: 1432-1041
    Keywords: Key words Methotrexate ; Rheuma; Bayesian estimation ; pharmacokinetic parameters ; P-PHARM software
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract  This paper describes a methodology to calculate methotrexate (MTX) pharmacokinetic parameters after intramuscular administration using two samples and the population parameters. Total and free MTX were measured over a 36-h period in 56 rheumatoid arthritis patients; 14 patients were studied after a two-dose scheme at 15-day intervals. The Hill equation was used to relate the free MTX to the total MTX changes in plasma concentrations, and a two-compartment open model was used to fit the total MTX plasma concentrations. A non-linear mixed effect procedure was used to estimate the population parameters and to explore the interindividual variability in relation to the following covariables: age, weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count, creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint count, and Ritchie’s articular index. Population parameters were evaluated for 40 patients using a three-step approach. The population average parameters and the interindividual variabilities expressed as coefficients of variation (CV%) were: CL, 6.94 l ⋅ h−1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h−1 (47.7%); k21, 0.0769 h−1 (61.6%); ka, 4.31 h−1 (58%); Emax, 1.12 μmol ⋅ l−1 (19.7%); γ, 0.932 (12.3%); and EC50, 2.14 μmol ⋅ l−1 (27.3%). Thirty additional data sets (16 new patients and 14 patients of the previous population but treated on a separate occasion) were used to evaluate the predictive performance of the population parameters. Twelve blood samples were collected from each individual in order to calculate individual parameters using standard fitting procedures. These values were compared to the ones estimated using a Bayesian approach with population parameters as a priori information together with two samples, selected from the individual observations. The results show that the bias was not statistically different from zero and the precision of these parameters was excellent.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Methotrexate ; Rheuma ; Bayesian estimation ; pharmacokinetic parameters ; P-PHARM software
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This paper describes a methodology to calculate methotrexate (MTX) pharmacokinetic parameters after intramuscular administration using two samples and the population parameters. Total and free MTX were measured over a 36-h period in 56 rheumatoid arthritis patients; 14 patients were studied after a two-dose scheme at 15-day intervals. The Hill equation was used to relate the free MTX to the total MTX changes in plasma concentrations, and a two-compartment open model was used to fit the total MTX plasma concentrations. A non-linear mixed effect procedure was used to estimate the population parameters and to explore the interindividual variability in relation to the following covariables: age, weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count, creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint count, and Ritchie's articular index. Population parameters were evaluated for 40 patients using a three-step approach. The population average parameters and the interindividual variabilities expressed as coefficients of variation (CV%) were: CL, 6.94 l · h-1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h-1 (47.7%); k21, 0.0769 h-1 (61.6%); ka, 4.31 h-1 (58%); Emax, 1.12 μmol · l-1 (19.7%); γ, 0.932 (12.3%); and EC50, 2.14 μmol · l-1 (27.3%). Thirty additional data sets (16 new patients and 14 patients of the previous population but treated on a separate occasion) were used to evaluate the predictive performance of the population parameters. Twelve blood samples were collected from each individual in order to calculate individual parameters using standard fitting procedures. These values were compared to the ones estimated using a Bayesian approach with population parameters as a priori information together with two samples, selected from the individual observations. The results show that the bias was not statistically different from zero and the precision of these parameters was excellent.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1619-7089
    Keywords: Positron emission tomography ; 11C-amino acids ; 18F-fluorodeoxyglucose ; Prolactinoma ; Salivary gland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aspects of metabolism in prolactinomas were investigated by positron emission tomography using l-[1-11C]tyrosine, l-[methyl-11C]methionine and 18F-fluorodeoxyglucose (18FDG). Using l-[1-11C]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocryptine. At 18 h after bromocryptine intervention, l-[1-11C]tyrosine uptake into tumour was reduced with 28% (P〈0.07). A correlation analysis of the bromocryptine-induced decrease in l-[1-11C]tyrosine uptake and the reduction of serum prolactin levels indicated that the action of bromocryptine on prolactin synthesis and prolactin release is not coupled. In the untreated situation, the four patients were investigated with 18FDG as well, but the prolactinomas could not be visualized. Three untreated patients were studied with l-[methyl-11C]methionine. The tumour-imaging potential of l-[methyl-11C]methionine and l-[1-11C]tyrosine appeared to be nearly equivalent for prolactinomas. Unlike prolactinoma tissue, the salivary glands showed a pronounced preference for l-[1-11C]tyrosine as compared to l-[methyl-11C]methionine. l-[1-11C]tyrosine is a valuable tool to obtain information on the metabolism and treatment of prolactinomas.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1572-9508
    Keywords: camera ; 10 micron ; Saturn
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract This paper presents the general features of the “C10μ” camera, now in routine operation at the CFHT, with initial results on CVF observations of the C2H2 and C2H6 bands and the continuum in the atmospher e of Saturn.
    Type of Medium: Electronic Resource
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