Cancer chemotherapy and pharmacology · 2011
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.
СтатьяМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Scheulen Max E, Saito Kaku, Hilger Ralf A, Mende Bastian, Zergebel Christopher, Strumberg Dirk
Аннотация
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.
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.