Authors: YookHwan Noh HyeongSeok Lim JinA Jung Tae Hun Song KyunSeop Bae
Publish Date: 2014/11/07
Volume: 75, Issue: 1, Pages: 97-109
Abstract
Blood samples were collected from three phase I studies in which fiftytwo patients received oral HM78136B tablets 05–32 mg once daily for 2 weeks and another 20 patients received oral HM78136B tablets 12 16 18 24 mg in fasting 12 patients or fed eight patients state once daily for 4 weeks Nonlinear mixed effect modeling was employed to develop the population pharmacokinetic modelHM78136 PK was ascribed to a twocompartment model and HM78136M1/M2 PK to onecompartment model HM78136 oral absorption was characterized by firstorder input absorption rate constant 145 ± 023 h−1 The central volume of distribution 185 ± 127 L was influenced significantly by body weight The absorption rate constant was influenced by food The typical HM78136 apparent clearance was 345 L/h 294 CV with an apparent peripheral volume of distribution of 164 L 535 CV Other covariates did not significantly further explain the PKs of HM78136The proposed model suggests that HM78136 PKs are consistent across most solid tumor types and that the absorption process of HM78136 is affected by the fed state before dosing HM78136 PKs are not complicated by patient factors other than body weight
Keywords: