Pharmacologic/pharmacokinetic evaluation of emesis induced by analogs of RSU 1069 and its control by antiemetic agents.
Int J Radiat Oncol Biol Phys
; 22(3): 549-51, 1992.
Article
em En
| MEDLINE
| ID: mdl-1531213
ABSTRACT
RB 6145, the ring-opened analog of RSU 1069, and PD 130908, the desoxy ring-opened analog of RSU 1069, were compared to RSU 1069 for their emetic potential in dogs. When RB 6145 and PD 130908 were administered intravenously at doses ranging from 20% to 50% of the mouse equivalent maximum tolerated dose (MTD), both analogs were less emetic than RSU 1069 on a molar basis. Furthermore, the 5HT3 antagonist ondansetron prevented emesis at doses as high as 75% of the MTD. The reactivity, and hence the emetic liability of these compounds, is thought to be mediated by formation of the corresponding aziridine intermediate. In mouse plasma, both analogs rapidly converted to two products, the reactive aziridine and a stable oxiazolidinone species formed upon reaction with bicarbonate in the blood. A positive correlation exists between the amounts of aziridine formed by these analogs and their emetic potential.
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Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
/
Vômito
/
Misonidazol
/
Antieméticos
/
Nitroimidazóis
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article