URINARY 5-HIAA EXCRETION IN RATS AFTER CHRONIC ADMINISTRATION OF CYCLOPHOSPHAMIDE

Cyclophosphamide causes nausea and vomiting in 60-90% of patients. Whi lst the initiating factor of the emesis produced by cyclophosphamide i s unknown, biotransformation of the drug has important consequences on emetic potency. At least 30 degradation products of cyclophosphamide have been identified but it is unclear which of these contributes to e mesis or whether they cause the release of some endogenous emetic fact ors. In order to elucidate whether 5-hydroxytryptamine (5-HT) is relea sed from the gut mucosa following cyclophosphamide administration, the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA) was investi gated in rats. Chronic administration of cyclophosphamide (4 weeks x 1 0 mg/kg, i.p.) significantly increased urinary 5-HIAA excretion in rat . There were no significant abnormal values in terms of s-GOT, GPT or LDH. The histopathology studies revealed only marginal changes to the mucosa in the rat intestine. It is concluded that the increased amount of 5-HIAA in rat urine induced by cyclophosphamide was derived from d egranulated 5-HT from EC cells in the gut mucosa This provides further support for the hypothesis that 5-HT is involved in cyclophosphamide- induced emesis in emetic species.