Genetic polymorphism-based oxcarbazepine quantitative pharmacological model and construction method thereof

By establishing a quantitative pharmacological model of oxcarbazepine based on genetic polymorphism, the problem of large differences in the concentration of oxcarbazepine in children's epilepsy is solved, and the formulation of individualized drug use plans is realized, which improves the safety and effectiveness of treatment.

CN119650097AActive Publication Date: 2025-03-18SHENZHEN CITY BAOAN DISTRICT MATERNAL & CHILD HEALTH HOSPITAL
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Patent Information

Application Number
CN202411702476.X
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-26
Publication Date
2025-03-18
Estimated Expiration
2044-11-26

AI Technical Summary

Technical Problem

Due to the fact that the metabolic enzyme system and organ functions in the body have not yet fully developed, the blood concentration of oxcarbazepine varies greatly between individuals, which may lead to treatment failure or adverse reactions.

Method used

The nonlinear mixed effect model method was used, combined with classic pharmacokinetic theory and statistical principles, and the population pharmacokinetic model of the active metabolite MHD of oxcarzepine was established, and the effects of physiological factors, combined medication and genetic factors on pharmacokinetic characteristic parameters were investigated. The MHD trough concentration under different dosage regimens was predicted through Monte Carlo simulation method, and dose recommendations were proposed for patients in different subgroups.

Benefits of technology

Accurate prediction of individual differences in oxcarbazepine treatment is achieved, and safe, effective and individualized medication regimens are provided, reducing the risk of treatment failure and adverse reactions.

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Abstract

The invention discloses an oxcarbazepine quantitative pharmacological model based on genetic polymorphism and a construction method thereof, and belongs to the field of pharmacokinetics. The model construction method comprises the following steps: collecting steady-state blood drug valley concentration data and clinical data of an epileptic child patient, establishing a population pharmacokinetic model of oxcarbazepine active metabolites by adopting a nonlinear mixed effect model method, and quantitatively investigating the influence of physiological factors, combined medication and genetic factors on pharmacokinetic characteristic parameters of drugs; and finally, performing internal verification and evaluation on the model by using a goodness-of-fit diagram, a bootstrap method and visual prediction inspection. The quantitative pharmacological model constructed by the method has stable and accurate prediction performance; according to the present invention, the weight and the gene polymorphism ABCC2rs2273697 are determined as the effective covariants affecting MHD CL / F, and the oxcarbazepine dosage optimization scheme is established based on the weight and the genotype of the patient so as to improve the treatment effect and avoid the adverse reaction;
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