The effect of food on the pharmacokinetics of S-1 after single oral administration to patients with solid tumors

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
G J PetersJan H M Schellens

Abstract

The purpose is to determine the effect of food on the bioavailability of S-1, an oral formulation of the 5-fluorouracil (5FU) prodrug Ftorafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), a dihydropyrimidine dehydrogenase inhibitor, and oxonic acid (an inhibitor of 5FU phosphoribosylation in normal gut mucosa) in a molar ratio of 1:0.4:1. Eighteen patients received a single dose of S-1 of 35 mg/m(2) with (535-885 kcal) or without food in a crossover study design: in arm A without breakfast on day -7 and with breakfast on day 0 and in arm B the reversed sequence. Blood samples were taken before and after S-1 administration. This food effect was evaluated according to the Food and Drug Administration guidelines using log-transformed data. Pharmacokinetic parameters for 5FU without breakfast were as follows: Tmax, 107 min; Cmax, 1.60 microm; area under the plasma concentration-time curve (AUC) 441 microm x min; and T(1/2), 104 min. Fasting decreased Tmax of FT, 5FU, CDHP, and oxonic acid significantly (P < 0.006) and increased the Cmax (P < 0.013). The food/fast ratio for the AUC of FT was not different, which for 5FU was 0.84 (P = 0.041), for CDHP was 0.89 (P = 0.191), for oxonic acid was 0.48 (P < 0.0005), and for cyanuric acid,...Continue Reading

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Citations

Jun 17, 2011·Future Oncology·Mariela BlumJaffer A Ajani
Jan 13, 2012·Expert Opinion on Drug Delivery·Koh MiuraIwao Sasaki
Jan 27, 2016·Indian Journal of Medical and Paediatric Oncology : Official Journal of Indian Society of Medical & Paediatric Oncology·Eriseld KrasniqiVincenzo Formica
Sep 8, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jaffer A AjaniPeter Urrea
Apr 6, 2017·Expert Opinion on Drug Delivery·Koh MiuraRyuichi Katakura
Oct 14, 2009·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Yuan GuChangxiao Liu

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