PURPOSE: @entity4672 is an orally active aromatase inhibitor for the treatment of @entity0 . The objectives of this study were to examine the pharmacokinetic profile of @entity4672 in Japanese subjects and to identify factors that influence variability in the pharmacokinetics of @entity4672 using population pharmacokinetic (PPK) analysis. METHODS: Twenty-five healthy postmenopausal Japanese @entity1 were enrolled in the study and received 2.5  mg @entity4672 once daily for 14 or 28  days. A PPK model was developed using NONMEM software. Age, body @entity353 ( @entity353 ), @entity6571 , ALT, total @entity648 , serum @entity1011 (CRE), and genotype of @entity5944 were studied as covariates. @entity1815 , @entity19517 , and @entity53 in plasma were measured as pharmacodynamic markers. RESULTS: @entity5944 genotype, CRE, and @entity6571 were significant covariates for apparent systemic clearance (CL/F), and @entity353 was a significant covariate for apparent distribution volume (Vd/F). Population mean estimates of CL/F and Vd/F in subjects without @entity5944 mutation were 1.03       (CRE/0.70)(-1.27)       ( @entity6571 /17.5)(-0.793)   L/h and 94.2       ( @entity353 /51.1)(1.12)   L respectively. CL/F in subjects possessing 1 and 2 @entity5944 mutation alleles were 84.3% and 44.8% of the value in the subjects without mutation respectively. @entity172 levels fell to below detection limits in most subjects after @entity4672 administration. Three mild and transient adverse events (upper respiratory tract @entity32 , @entity4841 , and @entity391 ) were reported in the study. CONCLUSIONS: @entity5944 genotype largely influences CL/F of @entity4672 . Genetic polymorphism of @entity5944 and body @entity353 will be causes of ethnic difference in PK. However, dose adjustment is not necessary, because of the wide therapeutic range.

Population pharmacokinetic analysis of @entity4672 in Japanese postmenopausal XXXX .

@entity1 :: ('9606', 'Species') :: ['women'] @entity172 :: ('MESH:D004967', 'Chemical') :: ['Estrogen'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity4672 :: ('MESH:C067431', 'Chemical') :: ['letrozole', 'Letrozole'] @entity19517 :: ('MESH:C017296', 'Chemical') :: ['estrone sulfate'] @entity6571 :: ('26503', 'Gene') :: ['AST'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity353 :: ('MESH:D015431', 'Disease') :: ['WT', 'weight'] @entity5944 :: ('1548', 'Gene') :: ['CYP2A6'] @entity648 :: ('MESH:D001663', 'Chemical') :: ['bilirubin'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol'] @entity1815 :: ('MESH:D004970', 'Chemical') :: ['Estrone'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity4841 :: ('MESH:D018771', 'Disease') :: ['arthralgia']
@entity1 :: (9606,Species) :: ['women']
