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 @entity1487 pharmacokinetics following oral UFT administration. A population study in 30 @entity1 with XXXX .

@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']
@entity0 :: (MESH:D001943,Disease) :: ['advanced breast cancer']
