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.
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Brasch, R. C. (1983) Radiology 147, 781–788.
Brasch, R. C., London, D. A., Wesbey, G. E., Tozer, T. N., Nitecki, D. E., Williams, R. D., Doemeny, J., Tuck, L. D., Lallemand, D. P. (1983) Radiology 147, 773–779.
Brasch, R. C., Nitecki, D. E., Brant-Zawadzki, M., Enzmann, D. R., Wesbey, G. E., Tozer, T. N., Tuck, L. D., Cann, C. E., Fike, J. R., Sheldon, P. (1983) AJNR 4, 1035–1039.
Wesbey, G. E., McNamara, M. T., Higgins, C. B., Lipton, M. J., Sievers, R., Engelstad, B. L., Ehman, R., Lovin, B. L., Brasch, R. C. Proceedings of the Association of University Radiologists Annual Meeting, May 6, 1984, p. 45 (abstract).
Ehman, R., Wesbey, G. E., Brasch, R. C. Abstract of paper presented at the Annual Meeting of the Radiological Society of North America, Chicago, Ill., November 19, 1983.
Couet, W. R., Eriksson, U. G., Tozer, T. N., Tuck, L. D., Wesbey, G. E., Nitecki, D., Brasch, R. C. (1984) Pharm. Res. 203–209.
Kosman, D. J., Hsia, J. C., Piette, L. H. (1969) Arch. Biochem. Biophys. 133, 29–37.
Chou, D., Polnaszek, C. F., Yost, Y., Leppik, I. E., Holtzman, J. L. (1981) Mol. Pharmacol. 20, 647–680.
Rozantsev, E. G. (1970) in: Free Nitroxyl Radicals (translated by Hazzard, B. J.) Plenum Press, New York.
Osborne, C. A., Low, D. G., Finco, D. R. (1972) in: Canine and Feline Urology. W. B. Saunders, Philadelphia.
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Couet, W.R., Eriksson, U.G., Brasch, R.C. et al. Pharmacokinetics of Two Prototype Nitroxide Spin Labels for Contrast Enhancement in Magnetic Resonance Imaging. Pharm Res 2, 69–72 (1985). https://doi.org/10.1023/A:1016334510417
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DOI: https://doi.org/10.1023/A:1016334510417