Effect of cyclophosphamide on the activity and distribution of pentobarbital in rats

Cyclophosphamide (CP) injected at different treatment schedules into CD male rats, prolongs narcosis after either parenteral or oral administration of pentobarbital. However, it takes 7 days before any change appears after CP pretreatment. The level of pentobarbital in blood and brain at different times after injection was higher in CP pretreated than in untreated animals. Since previous studies reported a decreased rate of inactivation of drugs after treatment with cytotoxic agents, experiments were performed to ascertain whether, beside the impairment of the metabolism, the animals respond differently to the same brain concentration of pentobarbital.