Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estracyt(R) is an antimitotic drug used 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 retching episodes and 7.5+/-1.3 vomiting episodes during a 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 retching and vomiting episodes 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 during treatment with Estracyt.
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PMID:[Effect of the 5-HT3 receptor antagonist granisetron on estramustine phosphate sodium (Estracyt)-induced emesis in ferrets]. 2072 8

Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive "pica" behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting.
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PMID:The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator. 2687 16