Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI

Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods. Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5. SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p