Abstract
Summary
Chloramphenicol pretreatment reduced the lethality of cyclophosphamide in vivo and resulted in an increased time of mean death and a higher mean lethal dose. Chloramphenicol pretreatment decreased the in vivo conversion of cyclophosphamide to a metabolite capable of alkylation. After pretreatment with chloramphenicol, a decreased amount of activated product appeared in the urine during 90 min and blood levels of active metabolite were less when measured after 90 min. In vitro chloramphenicol decreased the metabolism of cyclophospamide 50% at approximately 10-3 M. It is concluded that the protection afforded animals by chloramphenicol after treatment with lethal levels of cyclophosphamide is due to an inhibition of microsomal drug-metabolizing enzymes which are responsible for the in vivo activation of cyclophosphamide.
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