Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin.
The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma.
Laurent
F
F
Laboratoire de Biochimie Appliquée, Faculté des Sciences Pharmaceutiques, Toulouse, France.
Canal
P
P
Soula
G
G
D000818:Animals; D008175:Lung Neoplasms / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*
D008543:Melanins; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole