Irinotecan (Campto^R) Pharmacokinetics and Metabolism in Patients with Elevated Serum Bilirubin Levels
Pages 67-72
Najia Mansoor, Rafeeq Alam Khan, Johannes Schueller, Dagmar Ettlinger, Philipp Buchner, Martin Czejka and Tasneem Ahmad

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.02.4

Published: 15 April 2016 

Abstract: In this study, we have calculated and reported the pharmacokinetics of irinotecan and its active metabolite, SN-38, in patients with increased plasma bilirubin levels. Four patients suffering from metastatic colorectal cancer (CRC) with high bilirubin levels (0.7 to 15 mg/dl) were selected for our study. These patients were being treated by CPT -11 (Irinotecan) in the hospital setup. To all four patients, CPT-11 was administered as a 60 min IV- infusion (180 mg/m², total dose 339 ± 32 mg). Blood samples were collected at 0, 15, 30, 45, 60, 90,120, 180, 240, 300 and 360 minutes after the drug administration. The drug and its pharmacologically active metabolite, SN38 were quantified in these samples by an HPLC method. The blood level profiles were analyzed for their PK behavior by Kinetica® software system. SN 38 levels were found to be decreasing with increasing bilirubin values. The possible rationalizing for lower SN38 levels with elevated bilirubin levels might be some liver impairment which slows the metabolic conversion of irinotecan into SN-38.

Keywords: Irinotecan (CPT-11), SN-38, Bilirubin, liver impairment, Pharmacokinetics, DLT.