SN38glukuronidiksi

SN38glucuronide is a metabolite of irinotecan, a widely used chemotherapy drug. Irinotecan itself is a prodrug, meaning it needs to be converted into its active form within the body to exert its therapeutic effects. This conversion process primarily occurs in the liver, where irinotecan is hydrolyzed by carboxylesterases to SN38.

SN38 is the pharmacologically active cytotoxic agent responsible for the anticancer activity of irinotecan. It functions by inhibiting topoisomerase I, an enzyme crucial for DNA replication and repair. This inhibition leads to DNA damage and ultimately cell death, particularly in rapidly dividing cancer cells.

However, SN38 is highly toxic and poorly soluble, which limits its direct administration. To overcome these limitations, the body further metabolizes SN38 into SN38glucuronide through a process called glucuronidation, mediated by the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1). SN38glucuronide is a more water-soluble and less toxic conjugate that is primarily excreted in the bile and urine.

The activity of UGT1A1 plays a significant role in the pharmacokinetics and toxicity of irinotecan. Individuals with reduced UGT1A1 activity, often due to genetic variations, may accumulate higher levels of SN38, leading to increased risk of severe side effects such as diarrhea and neutropenia. Conversely, individuals with highly active UGT1A1 may clear SN38 more rapidly, potentially reducing its efficacy. Therefore, UGT1A1 genotyping is sometimes used to guide irinotecan dosing.