Prediction of Irinotecan Pharmacokinetics by Use of Cytochrome P450 3A4 Phenotyping Probes

has been approved for use as a first- and second-line treat-ment for colorectal cancer. The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, includ-ing cytochrome P450 3A4 (CYP3A4) and uridine diphos-phate glucuronosyltransferase 1A1 (UGT1A1). We prospec-tively explored the relationships between CYP3A phenotype, as assessed by erythromycin metabolism and midazolam clearance, and the metabolism of irinotecan and its active metabolite SN-38. Methods: Of the 30 white cancer patients, 27 received at least two treatments with irinotecan adminis-tered as one 90-minute infusion (dose, 600 mg) with 3 weeks between treatments, and three received only one treatment. Before the first and second treatments, patients underwent an erythromycin breath test and a midazolam clearance tes