Effect of food and a proton pump inhibitor on the pharmacokinetics of S-1 following oral administration of S-1 in patients with advanced solid tumors

Purpose S-1 is a novel oral fluoropyrimidine comprised of FT and two modulators, gimeracil (CDHP) and oteracil potassium (Oxo). This study investigated the food effects on the pharmacokinetics (PK) of Oxo, other components of S-1, and their metabolites at different gastric pH adjusted by proton pump inhibitor (PPI). Methods Patients with and without PPI were treated with S-1 at 30 mg/m 2 twice daily orally on days 1–7 under either fed or fasting condition, and then were crossed over to fasting/fed conditions on days 15–21 with washout on days 8–14 and 22–28. Results The study enrolled 55 patients including 27 PK-evaluable patients. For the single-dose and multiple-dose pharmacokinetics, the administration of S-1 under fed conditions resulted in decreased exposure to Oxo relative to fasting administration. There was a marginal decrease in exposure to CDHP and 5-FU under fed versus fasting conditions, although FT exposure was not altered by food, which demonstrated lack of food effect. PPI administration together with S-1 did not significantly change its bioavailability. Conclusions Oxo exposure was reduced under fed compared to fasting condition. To increase the bioavailability of S-1, the administration of S-1 under fasting condition was more effective in the western countries.