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Drug Metabolism and Disposition Fast Forward
First published on April 23, 2009; DOI: 10.1124/dmd.109.027052

0090-9556/09/3707-1375-1377$20.00
DMD 37:1375-1377, 2009

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SHORT COMMUNICATION

Pharmacokinetics of 5-Fluorouracil in Elderly Japanese Patients with Cancer Treated with S-1 (a Combination of Tegafur and Dihydropyrimidine Dehydrogenase Inhibitor 5-Chloro-2,4-dihydroxypyridine)

K. Fujita, H. Nakayama, W. Ichikawa, W. Yamamoto, H. Endo, F. Nagashima, R. Tanaka, T. Miya, Y. Sunakawa, K. Yamashita, K. Mizuno, H. Ishida, K. Araki, M. Narabayashi, K. Miwa, Y. Ando, Y. Akiyama, K. Kawara, T. Hirose, and Y. Sasaki

Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Hidaka, Saitama, Japan (K.F., H.N., W.I., W.Y., H.E., F.N., R.T., T.M., Y.Su., K.Y., K.Miz., H.I., K.A., M.N., K.Miw., Y.An., Y.Ak., K.K., T.H., Y.Sa.); and Project Research Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan (K.F., F.N., Y.Ak., Y.Sa.)

S-1 is an oral anticancer agent that combines tegafur, a prodrug of 5-fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase. We examined the effects of aging on the pharmacokinetics of the components of S-1. The median area under the concentration-time curve (AUC) of active 5-FU did not significantly differ between 10 patients 75 years or older and 53 patients younger than 75 years (P = 0.598, Mann-Whitney U test). It is interesting to note that the median oral clearance of tegafur in patients 75 years or older was significantly lower than that in patients younger than 75 years (P = 0.011). Furthermore, the median AUC of CDHP was significantly higher in patients 75 years or older than in those younger than 75 years (P = 0.004). This effect was caused by reduced renal function in the elderly, because CDHP is excreted in the urine by glomerular filtration. The opposing effects of aging on the oral clearance of tegafur and the AUC of CDHP may offset each other, leading to unchanged systemic exposure of 5-FU.

Address correspondence to: Dr. Ken-ichi Fujita, Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. E-mail: fujitak{at}saitama-med.ac.jp






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