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Cell status : dead or alive? (1996)

Brown, J. Martin

[s.l.] : Nature Publishing Group

Nature medicine 2 (1996), S. 1055-1055

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ISSN: 1546-170X

Source: Nature Archives 1869 - 2009

Topics: Biology , Medicine

Notes: [Auszug] To the editor — In the July issue of Nature Medicine, Domenico Delia and colleagues reported that the sensitivity of human lymphoblastoid cells to γ-radiation was markedly affected by their p53 status, whereas this was not the case for their sensitivity to the chemotherapeutic agent ...

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1038/nm1096-1055b

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Structure-pharmacokinetic relationships for misonidazole analogues in mice (1981)

Workman, Paul ; Brown, J. Martin

Springer

Cancer chemotherapy and pharmacology 6 (1981), S. 39-49

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ISSN: 1432-0843

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary We have compared the mouse pharmacokinetics of six analogues of the hypoxic cell sensitizer misonidazole (MISO). The analogues were all uncharged and similar in redox potential, but widely different in octanol-water partition coefficient (range 0.026–1.5). Lipophilic analogues were cleared mainly by metabolism and non-linear elimination kinetics were seen at high doses. Hydrophilic analogues, including desmethylmisonidazole, SR-2508, and SR-2555, were removed principally by renal clearance exhibiting linear elimination kinetics. Lipophilic analogues were cleared more rapidly after hepatic microsomal enzyme induction by phenobarbitone, whereas the kinetics of hydrophilic analogues were unaffected. Low-dose clearance was similar for most of the analogues. But the hydrophilic SR-2555 was cleared twice as quickly as MISO, and the liphophilic Ro 07-0913 seven times faster than MISO. Plasma protein binding was low for all the analogues. The significance of these results for the predictive value of the mouse as a model for man is discussed.