前立腺癌治療薬エストラムスチン(エストラサイト®)で誘発されるフェレットにおける悪心・嘔吐に対する5-HT3 受容体拮抗薬の効果

Abstract

Estracyt® is an antimitotic drugused for the treatment of prostate cancer, and its most common adverse effects are nausea and vomiting. In this study, we investigated the effect of a 5-HT3 receptor antagonist, granisetron, on emesis induced in ferrets by estramustine phosphate sodium (EMP), the active ingredient of Estracyt. To clarify the mechanism of action of EMP-induced emesis, we also investigated the effect of EMP on the release of serotonin (5-HT) in the isolated rat ileum. EMP (3 mg/kg, per os) induced 75.3±10.2 retchingepisodes and 7.5±1.3 vomitingepisodes duringa 2-h observation period. The latency to the first emetic response was 58.0±13.5 min. Granisetron (0.1 mg/kg, per os) administered 1 h before the administration of EMP reduced the number of EMP-induced retchingand vomitingepisodes to 1.3±1.3 and 1.0±1.0, respectively, and prolonged the latency by a factor of almost two. EMP (10−5 and 10−4 M) increased 5-HT release from isolated rat ileum, and 10 −7 M granisetron almost completely inhibited the increase induced by 10−4 M EMP. These results suggest that EMP induces nausea and vomiting via 5-HT release from the ileum, and that 5-HT3 receptor antagonists may be useful to prevent gastrointestinal adverse effects that occur duringtreatment with Estracyt.