Hepatic Imaging May Predict Drug Pharmacokinetics

Anti-cancer drug irinotecan has narrow therapeutic window

TUESDAY, Sept. 12 (HealthDay News) -- Functional hepatic nuclear imaging and genotyping may be useful in predicting the pharmacokinetics of the anti-cancer drug irinotecan, which has a narrow therapeutic window, according to a study in the Sept. 10 issue of the Journal of Clinical Oncology.

Michael Michael, M.D., of the Peter MacCallum Cancer Centre in Victoria, Australia, and colleagues performed functional hepatic nuclear imaging in 16 patients with advanced colorectal cancer using substrates of the multidrug resistance transporters P-glycoprotein, MRP1, and MRP2. They also performed genotyping of the ABCB1 (P-glycoprotein) and UGT-1A1 genes, which they noted influenced irinotecan pharmacology. Patients were treated with irinotecan, fluorouracil and folinic acid.

The researchers found that the one hour hepatic retention time of one of the imaging agents showed a significant association with baseline serum bilirubin. The area under the curve of SN-38, the active metabolite of irinotecan, was also positively correlated with the one hour retention of both imaging agents. The excretion of one of the imaging agents was prolonged in patients with the ABCB1 exon 26 TT variant allele, according to the study.

"Functional imaging of hepatic uptake and excretory pathways may have potential to predict irinotecan pharmacokinetics," Michael and colleagues concluded.

The study was funded in part by Pfizer Proprietary Ltd.

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