PURPOSE: The pharmacokinetics of @entity16229 , @entity1487 ( @entity1487 ) and @entity5537 were investigated in order to built a population pharmacokinetic model for the anticancer drug UFT, administered with @entity4181 and @entity1206 . METHODS: A total of 31 @entity1 with metastatic @entity0 were treated with escalating oral doses of UFT (300 to 500 mg per day) plus @entity4181 (90 mg per day) in combination with intravenous @entity1206 (15 to 25 mg/m(2)). Concentration-time data were obtained on days 1, 8, 15 and 21 of cycle 1. RESULTS: Of the 31 @entity1 treated, 30 were available for the pharmacokinetic analysis. Ftorafur, 5FU and @entity5537 appeared rapidly in plasma and showed large interpatient variations. Ftorafur concentrations were higher than those of 5FU and @entity5537 . AUC significantly increased between day 1, and days 8, 15 and 21. Ftorafur C(max) and AUC values were proportional to UFT dose, whereas C(max) and AUC values of 5FU and @entity5537 were not linearly related to UFT dose. The pharmacokinetics of ftorafur were ascribed to a two-compartment open model in which 5FU was produced from the central compartment. The absorption and exponential distribution rate constants were assumed equal. The effect of @entity5537 on 5FU elimination was straightforward, since no reasonable curve-fitting could be obtained for 5FU data when this covariate was not taken into account. The @entity5537 concentration inducing a 50% reduction in 5FU elimination was 2.67 micro mol.l(-1). This result confirms the important role played by @entity5537 as a competitive inhibitor of 5FU catabolism. CONCLUSION: A pharmacokinetic model for ftorafur and 5FU was developed and should be useful to further study drug interactions and establish dosing guidelines.

Modelling of ftorafur and XXXX pharmacokinetics following oral UFT administration. A population study in 30 @entity1 with @entity0 .

@entity4181 :: ('MESH:D002955', 'Chemical') :: ['leucovorin'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity1206 :: ('MESH:C030852', 'Chemical') :: ['vinorelbine'] @entity16229 :: ('MESH:D005641', 'Chemical') :: ['ftorafur'] @entity5537 :: ('MESH:D014498', 'Chemical') :: ['uracil'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5FU', '5-fluorouracil']
@entity1487 :: (MESH:D005472,Chemical) :: ['5-fluorouracil']
