Shrew model maps how irinotecan triggers vomiting and which antiemetic combinations work best
- In Suncus murinus, irinotecan caused dose-dependent vomiting within 24 hours, but its active metabolite SN-38 did not; respiration was unaffected.
- Vagotomy blunted early emesis, and irinotecan raised c-Fos in brainstem, hypothalamic and limbic areas, with palonosetron dampening only the brainstem.
- Palonosetron was the best single drug; olanzapine combined with palonosetron plus aprepitant or dexamethasone beat monotherapy.
💡 Points
A shrew that vomits to irinotecan but not to SN-38 makes me ask what is actually driving it: gut-local exposure, or vagal signaling rather than the systemic metabolite? I'd want exposure measured alongside emesis before trusting the combination data. And olanzapine's added benefit in a shrew says little yet about sedation and tolerability margins in patients.
Investigation of the mechanisms and modulation of irinotecan‐induced emesis in Suncus murinus ↗