Abstract
Summary
The simultaneous administration of cyclophosphamide and pentobarbital resulted in a rapid onset of death for BALB/c mice. When the drugs were given 1 hr apart, in either order, the mice survived. Pentobarbital lethality was potentiated in a parallel manner by 375 mg cyclophosphamide/kg. Hexobarbital and phenobarbital successfully substituted for pentobarbital in eliciting enhanced lethality when administered with cyclophosphamide. Cyclophosphamide increased the duration of sedation elicited by each barbiturate. Pretreatment of mice with multiple phenobarbital injections diminished the lethal action of subsequent challenge with cyclophosphamide and pentobarbital. However, mice pretreated with phenobarbital were hyperreactive to cyclophosphamide alone. The 9000g liver supernatant fraction derived from cyclophosphamidetreated mice was about equal in metabolizing aminopyrine as was the 9000 g liver supernatant fraction derived from normal mice. Cyclophosphamide had a minor effect on the amount of pentobarbital recovered from mouse brain tissue 15 min after injection, compared to mice receiving pentobarbital alone.
The superb technical assistance of Mrs. A. Munson is gratefully acknowledged. W. C. R. was the recipient of an A. D. Williams Fellowship. The research upon which this publication was based was performed pursuant to Public Health Service contract No. NIH-NCI-C-69-2266 from the National Institutes of Health.
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