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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 46 (2000), S. 227-234 
    ISSN: 1432-0843
    Keywords: Key words ALIMTA ; Pemetrexed disodium ; Population pharmacokinetics ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the population pharmacokinetics of pemetrexed disodium in cancer patients enrolled in four different open-label, multicenter, nonrandomized phase II studies. Methods: Pemetrexed disodium was administered as a 10-min intravenous infusion (600 mg/m2) every 21 days. A total of four blood samples were to be collected each cycle per patient (n=103 patients) during cycles 1 and 3. Plasma concentration-time data were analyzed by nonlinear mixed-effect modeling using NONMEM to estimate pemetrexed disodium pharmacokinetic parameters (mean, and between- and within-patient variability) as well as relationships between the pharmacokinetic parameters and various patient-specific factors (demographic and physiologic data). Results/Conclusions: The pharmacokinetics of pemetrexed disodium were best characterized by a two-compartment model with initial distribution and terminal elimination half-lives of 0.63 h and 2.73 h, respectively. The typical value of systemic clearance (CL) in liters per hour included a relationship to creatinine clearance (CrCL) with a slope of 0.0292. Typical values of central volume (Vc), distributional CL (Q), and peripheral volume (Vp) were 11.3 l, 3.21 l/h, and 5.20 l, respectively. Between-patient variability was 19.6%, 15.6%, and 21.7% for CL, Vc, and Vp, respectively. A combined additive/proportional error model was used to describe residual variability, with a coefficient of variation of 23.7% for the proportional component and a standard deviation of 0.0410 μg/ml for the additive component. Significant patient-specific factors on CL were calculated CrCL, body weight, and to a lesser extent alanine transaminase and folate deficiency. Gender and body weight were significant factors on Vc while both body surface area and albumin were significant factors on Vp. In conclusion, population pharmacokinetic modeling revealed relationships between pharmacokinetic parameters and various patient specific factors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 50 (1993), S. 1357-1368 
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Mechanical scission of two typical perfluoropolyethers was investigated: Y, a copolymer of —CF(CF3)CF2O—, —CF2O—, and —CF(CF3)O—, and Z, a copolymer of —(CF2)nO—, with n = 1,2,3,4. Undiluted polymers were subjected to prolonged shearing in a media mill with ZrO2 particles. A chemical extraction of the polar ZrO2 particles was carried out to collect adsorbed polar scission products. Mechanochemical scission products from both the Y and Z fluorocarbon polymers were identified by 19F-NMR. A significant amount of CF3CO2- was present after the milling and the primary functional groups formed at scissioned chain ends were —CO-2. A hydrodynamic expression was derived and the maximum extension rate was estimated to be in the range of 5 × 106 s-1. Initial degrees of polymerization were between 20 and 200, well below levels for which flow-induced scission is expected to occur. Final degrees of polymerization were less than 10, and the scission was noncentral and nonrandom in both polymers. © 1993 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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