Effects of oral administration of S-1 on the pharmacokinetics of SN-38, irinotecan active metabolite, in patients with advanced colorectal cancer

• Published in: Therapeutic drug monitoring Vol. 31; no. 3; p. 400
• Main Authors: Yokoo, Koji, Hamada, Akinobu, Tazoe, Kensuke, Sasaki, Yutaka, Saito, Hideyuki
• Format: Journal Article
• Language: English
• Published: United States 01.06.2009
• Subjects: Administration, Oral; Aged; Antineoplastic Agents, Phytogenic - pharmacokinetics; Camptothecin - analogs & derivatives; Camptothecin - pharmacokinetics; Colorectal Neoplasms - metabolism; Drug Combinations; Female; Fluorouracil - administration & dosage; Fluorouracil - metabolism; Humans; Male; Middle Aged; Oxonic Acid - administration & dosage; Oxonic Acid - pharmacology; Prodrugs - pharmacokinetics; Tegafur - administration & dosage; Tegafur - pharmacology
• ISSN: 1536-3694
• DOI: 10.1097/FTD.0b013e31819c67e5

Previous studies have assessed the efficacy and safety of combined treatment with irinotecan (7-ethyl-10-[4-[1-piperidino]-1-piperidino]carbonyloxycamptothecin, CPT-11) and S-1, containing tegafur, a prodrug of 5-fluorouracil, in the treatment of colorectal and gastric cancer. The objective of this study was to describe the interaction between CPT-11 and S-1 in 4 patients with colorectal cancer. Coadministration of S-1 changed the pharmacokinetic behavior of CPT-11 and its metabolites. In particular, maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC) of 7-ethyl-10-hydroxycampothecin (SN-38) was markedly decreased by coadministration of S-1. For SN-38, the median ratio of Cmax and AUC with S-1 to those without S-1 was median 0.34 (range 0.24-0.78) and 0.56 (range 0.23-0.68), respectively. A markedly difference in drug interaction among individual patients was observed. We conclude that the plasma concentration of SN-38 was decreased by oral administration of S-1 in patients with colorectal cancer. This observation might be important for clinical decisions regarding combination therapy.