KIH-802, an acetohydroxamic acid derivative of 2-nitroimidazole, as a new potent hypoxic cell radiosensitizer: radiosensitizing activity, acute toxicity, and pharmacokinetics.
The radiosensitizing activity, acute toxicity, and pharmacokinetics of a new hypoxic cell radiosensitizer, potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802), were compared with those of misonidazole (MISO) and etanidazole (SR-2508). The radiosensitizing activity of KIH-802 was slightly higher than that of MISO and SR-2508 in vitro and was similar to or slightly higher than that of MISO or SR-2508 in vivo. The acute toxicity of KIH-802 was slightly higher than that of MISO. The concentrations of KIH-802 in the brains and peripheral nerves of mice were as low as those of SR-2508 and lower than those of MISO.
Sasai
K
K
Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
Shibamoto
Y
Y
Takahashi
M
M
Zhou
L
L
Hori
H
H
Nagasawa
H
H
Shibata
T
T
Inayama
S
S
Abe
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D017341:Etanidazole; D005260:Female; D006877:Hydroxamic Acids / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000860:Hypoxia / Q000473:pathology*; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008920:Misonidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors
D006877:Hydroxamic Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C057685:2-nitroimidazole-1-acetohydroxamic acid; D017341:Etanidazole; D008920:Misonidazole