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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and Metabolic Fate of Two Nitroxides Potentially Useful as Contrast Agents for Magnetic Resonance Imaging (1984)
    Springer
    Pharmaceutical research 1 (1984), S. 203-209 
    Details
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Paramagnetic nitroxyl-containing compounds have been useful as contrast agents in magnetic resonance imaging (MRI) experiments in animals. Preliminary information on the metabolic fate, pharmacokinetic behavior, stability in tissues, and chemical reduction of two prototypic nitroxides, PCA and TES, is presented. In the dog TES was eliminated more rapidly than PCA. More than 80 % of the dose of both nitroxides was recovered in urine within 6 hours. Nitroxides were reduced in vivo to their corresponding hydroxylamines. No other metabolite was observed. Measured reducing activity in tissue homogenates was greater in liver or kidney than in brain, lung or heart. In each tissue PCA was more stable than TES. PCA was also more resistant to reduction by ascorbic acid at physiologic pH. These preliminary results favor the use of PCA, a pyrrolidinyl nitroxide, over TES, a piperidinyl nitroxide, for MRI contrast enhancement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016317212601
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of Two Prototype Nitroxide Spin Labels for Contrast Enhancement in Magnetic Resonance Imaging (1985)
    Springer
    Pharmaceutical research 2 (1985), S. 69-72 
    Details
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two nitroxide spin labels called PCA and TES have been used experimentally as contrast enhancing agents in magnetic resonance imaging. Pharmacokinetic data for these nitroxides, after intravenous administration to three dogs at two dose levels (0.1 and 2.5 mmole/kg), are presented. In this dose range, the clearance (13 ml/ min-kg) and half-life (22 min) of PCA stayed almost constant while TES clearance decreased (28 to 12 ml/min-kg) and half-life increased (8 to 17 min) with dose. The urinary recovery, determined from the sum of the nitroxide and its corresponding hydroxylamine, was 85 to 90% for both PCA and TES. PCA was investigated in more detail because of its lower clearance value and its lack of dose-dependence. The major pathways of elimination are renal excretion and metabolic reduction to the corresponding hydroxylamine which is eliminated by renal excretion. We estimated renal clearance of both PCA (5.5 ml/ min-kg) and its hydroxylamine (3.7 ml/min-kg) to be close to glomerular filtration rate (4 ml/min-kg) in the dog, while the metabolic clearance (7.5 ml/min-kg) was slightly higher. Approximately 35 % of the administered dose of PCA was excreted unchanged and half was reduced in the body.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016334510417
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    Paper (German National Licenses)
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