A phase I study evaluating the relative bioavailability of S-1 capsules.

e13086 Background: S-1 is an oral, fixed-dose combination product comprised of tegafur (FT), a prodrug of 5-FU, and 2 modulators of 5-FU metabolism: gimeracil (CDHP) and oteracil (Oxo). S-1 is designed to provide oral delivery of 5-FU while reducing the rate of degradation of 5-FU and its conversion in the gastrointestinal tract to its toxic phosphorylated metabolite. The purpose of this study was to investigate the bioavailability of S-1 components and 5-FU after administration of standard S-1 capsules compared to an oral solution. Methods: Patients with advanced stage solid tumors received single oral doses of 50 mg S-1 capsule (2 × 25 mg capsules) or 50 mg S-1 oral solution (80 mL) on Day 1 and Day 8 in a randomized crossover fashion. Plasma samples were collected on Days 1 and 8 predose (0 hr) and at 0.25, 0.5, 1, 2, 4, 6, 8, 10, 24 and 48 hrs postdose. Single-dose pharmacokinetic (PK) parameters (AUC and Cmax) were determined for FT, 5-FU, CDHP, and Oxo. Results: 14 patients (3 men, 11 women) were en...