ArticleCurrent pharmaceutical design2025
Establishment of an Integrated Population Pharmacokinetic/ Pharmacodynamics Model of Apixaban in Chinese Healthy Population Adjusting for Key Genetic Variants.
Article in Current pharmaceutical design, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsTo improve the understanding of pharmacokinetic/pharmacodynamic (PK/PD) profiles of apixaban, supporting personalised drug prescriptions for future patients.
backgroundGenetic as well as nongenetic factors can affect the predictable PK and PD characteristics of apixaban.
objectiveEstablish a integrated popPK/PD model that adjusts for critical genetic variant.
methodsThe integrated PK/PD models was characterized on the basis of PK (apixaban blood concentration) and PD (prothrombin time (PT), activated partial thromboplastin time (APTT), and anti-FXa activity) data from 181 healthy Chinese volunteers. Other investigated covariate variables included: Meaningful intrinsic and extraneous determinants, correlated genetic factors (ABCG2, F13A1, C3, etc.). A total of 2877 PK concentration observations were included in the modeling dataset.
resultsThe PK model of apixaban is adopted by single compartment model with first-order oral absorption. The estimated values of total clearance rate (CL/F), apparent distribution volume (V/F), and absorption rate constant (KA) in the final model are 3.37 L/h, 28.2 L, and 0.781 1/h, respectively. The PK model includes significance covariates such as FOOD, RBC, WT, and gene (ABCG2). The PD model of apixaban is adopted by a linear direct effect model with additive error, which was used to describe the relationship between markers such as APTT, PT, anti-FXa,
conclusionWe established a comprehensive PK/PD model and used it to simulate markers level such as APTT, PT, and anti-FXa of apixaban. Individual predictive values with a dose of 2.5 mg are basically within the expected recommended range.
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