Effects of oral administration of S-1 on the pharmacokinetics of SN-38, irinotecan active metabolite, in patients with advanced colorectal cancer.
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.
Department of Pharmacy, Kumamoto University Hospital, Kumamoto University, Kumamoto 860-8556, Japan.
Koji
K
Yokoo
Akinobu
A
Hamada
Kensuke
K
Tazoe
Yutaka
Y
Sasaki
Hideyuki
H
Saito
D000284:Administration, Oral; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D011355:Prodrugs / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D011355:Prodrugs; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin