To establish a model for the prediction of initial standard and maintenance doses of warfarin for the Han Chinese population based on gene polymorphism: a multicenter study.

PURPOSE: The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype. METHODS: The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient's dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression. RESULTS: The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) - 0.273 × (CYP2C9*3) + 0.245 × (body surface area) - 0.003 × (age) - 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) - 0.214 × (CYP2C9*3) - 0.074 × (amine-iodine) - 0.003 × (age) - 0.077 × (statins) - 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose. CONCLUSION: The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.

Controlled Release Study on Bifidocin A from a Polyvinyl Alcohol/Chitosan Blend Particle-Based Biodegradable and Active Packaging Coupled with Mechanistic Assessment and Experimental Modeling.

On the basis of PVA-CS, which is incorporated with Bifidocin A, anti-microbial biodegradable films were prepared, characterized by their abilities to control the Bifidocin A's total release rate into foods as needed for packaging of active foods. This study aimed to explore the anti-microbial effects and release kinetics of active substances in polyvinyl alcoholchitosan (PVA-CS) particle composite films added with Bifidocin A. Pseudomonas fluorescens was used as indicator bacteria to evaluate the anti-microbial activity of the films. Fick's law, power law and negative exponential growth model were applied to further study the release kinetics of Bifidocin A. The results revealed that the composite films of PVA and CS had better mechanical properties and anti-microbial activity when the content of Bifidocin A was 50% with 1:1 PVA/CS, but it impairs the structure of the film, which can be resolved by including a suitable amount of grycerol. The anti-microbial was released faster at higher temperature and concentration of Bifidocin A, and the diffusion coeffcients increased significantlywith the increase of temperature and concentration. According to the thermodynamic parameters, the release of Bifidocin A was endothermic and spontaneous. High correlation factors (R² > 0.99) were acquired by fitting the release data of the Bifidocin A with the negative exponential growth model. The potential of Bifidocin A to deliver from the films into the food analog appropriately at low temperatures favored the obtained active films to be applied on food packaging, especially suitable for refrigerated foods.