Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription. People with variants of the UGT1A1 called TA7, also known as the "*28 variant", express fewer UGT1A1 enzymes in their liver. During chemotherapy, they effectively receive a larger than expected dose because their bodies are not able to clear irinotecan as fast as others. In studies this corresponds to higher incidences of severe neutropenia and diarrhea.[3]
SLOW METABOLISM=HOGERE DOSIS=DIARREE EN NEUTROPENIE