CN-121980980-A - Rayleigh Malun target control infusion analysis method and system

CN121980980ACN 121980980 ACN121980980 ACN 121980980ACN-121980980-A

Abstract

A target control infusion analysis method and system for a unit dose of a Rayleigh (Rayleigh) end-to-end (Malun) infusion system comprises the steps of constructing an individuation pharmacokinetic model by adopting a three-chamber model, characterizing plasma concentration response of the unit dose of the Rayleigh (Malun) by the individuation pharmacokinetic model, constructing an infusion pump control model, characterizing plasma drug concentration by a time function, defining a state variable for the infusion pump control model, calculating the plasma drug concentration state variable at the time t+delta t according to the plasma drug concentration state variable at the current time t and the drug infusion quantity in a time t+delta t interval, and determining the drug infusion rate required by the plasma drug concentration reaching the target concentration C T by the infusion pump control model by utilizing the plasma drug concentration state variable at the current time t and the plasma drug concentration state variable at the time t+delta t. The invention can realize individual medication, reduce occurrence of cardiovascular adverse events of patients and provide comfortable and safe infusion scheme for patients.

Inventors

LI HUIFEN
JIA JINTAI
WEN ZHE
YANG XIAOLI
LI JIAO

Assignees

长治医学院附属和济医院
长治医学院附属和平医院

Dates

Publication Date: 20260505
Application Date: 20240328

Claims (10)

1. A method of target controlled infusion analysis of rayleigh Malun comprising: constructing an individualized pharmacokinetic model by adopting a three-chamber model, and characterizing the plasma concentration response of the unit dose Rayleigh Malun by the individualized pharmacokinetic model; Constructing an infusion pump control model, wherein the infusion pump control model characterizes the plasma drug concentration through a time function, and parameters of the time function comprise the index sum of the plasma concentration to unit dose Rayleigh (Malun) response determined by the individuation pharmacokinetics model; Defining a state variable R i (t) for the infusion pump control model, and calculating the state variable of the plasma drug concentration at the moment t+delta t according to the state variable of the plasma drug concentration at the moment t and the drug infusion quantity in the interval from the moment t to the moment t+delta t; The infusion pump control model utilizes the plasma drug concentration state variable at the current time t and the plasma drug concentration state variable at the time t+Δt to determine the drug infusion rate required by the plasma drug concentration to reach the target concentration C T .
2. A method of analysis of target-controlled infusion of rayleigh Malun according to claim 1, wherein the decay equation of the personalized pharmacokinetic model is: Wherein P (t) is the plasma concentration response of the unit dose of the rimazolam, t is time, A j and lambda i are both pharmacokinetic model parameters, and s is the decay time length.
3. A method of rayleigh Malun-targeted infusion analysis as claimed in claim 2 wherein the rates of drug change of the central, first and second peripheral chambers in the personalized pharmacokinetic model are represented by differential equations: Where X 1 (t)、X 2 (t)、X 3 (t) is the drug dose in the central chamber, the first peripheral chamber, and the second peripheral chamber at time period P i , respectively, k 10 、k 12 、k 13 is the drug elimination rate constant from the central chamber to the outside, from the central chamber to the first peripheral chamber, and from the central chamber to the second peripheral chamber, k 21 is the drug elimination rate constant from the first peripheral chamber to the central chamber, and k 31 is the drug infusion rate at time t for the drug elimination rate constant ;E 1 ＝k 12 +k 13 +k 10 ;E 2 ＝k 21 ;E 3 ＝k 31 ;I i (t) from the second peripheral chamber to the central chamber.
4. A method of claim 3, wherein the plasma drug concentration C p is characterized by a time function of: The expression formula of the state variable R i (t) is: The time function characterized by plasma drug concentration is rewritten by state variable R i (t): The expression formula of the drug infusion quantity in the time t+delta t interval is as follows: Wherein P (t-t ') is the next dose change time interval, I represents a constant drug infusion rate, and I (t ') is the drug infusion rate at time t '.
5. The method of claim 4, wherein the expression of the drug dose in the central chamber, the first peripheral chamber, and the second peripheral chamber at time period P i is as follows: Wherein X 1 (0)、X 2 (0)、X 3 (0) is the dose of period P i at time 0, lambda 1 、λ 2 、λ 3 is the three-exponential mixing rate constant of drug decay, k 0 is the zero-order infusion equation of period Pi drug, bi represents the single injection dose infusion of period Pi drug ;D 1 ＝(λ 2 -λ 1 )(λ 3 -λ 1 );D 2 ＝(λ 1 -λ 2 )(λ 3 -λ 2 );D 3 ＝(λ 1 -λ 2 )(λ 2 -λ 3 ).
6. A method of analysis of Rayleigh Malun targeted infusion in accordance with claim 5, At the time of calculating rate=1 and initial R i (0) =0 prior to starting the control injection, plasma drug concentration at time Δt C p : At each iteration t+Δt, if there is no drug infusion, the plasma drug concentration C p (t+Δt) i＝0 at time t+2Δt is calculated: The drug injection rate I required from C p (t+Δt) to C T is: If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the desired C T .
7. A rayleigh Malun target-controlled infusion analysis system, comprising: The plasma concentration response characterization module is used for constructing an individualized pharmacokinetic model by adopting a three-chamber model, and characterizing the plasma concentration response of the unit dose of Malun by the individualized pharmacokinetic model; the system comprises a plasma drug concentration characterization module, an infusion pump control model, a blood plasma drug concentration analysis module and a blood plasma drug concentration analysis module, wherein the plasma drug concentration characterization module is used for constructing the infusion pump control model, and the infusion pump control model is used for characterizing the plasma drug concentration through a time function, and parameters of the time function comprise the index sum of the reaction of the plasma concentration determined by the individuation pharmacokinetics model to the Rayleigh Malun of unit dose; The state variable analysis module is used for defining a state variable R i (t) for the infusion pump control model, and calculating the state variable of the plasma drug concentration at the moment t+delta t according to the state variable of the plasma drug concentration at the moment t and the drug infusion quantity in the interval from the moment t to the moment t+delta t; And the drug infusion rate calculation module is used for determining the drug infusion rate required by the plasma drug concentration reaching the target concentration C T by using the plasma drug concentration state variable at the current time t and the plasma drug concentration state variable at the time t+delta t by the infusion pump control model.
8. The system of claim 7, wherein the plasma concentration response characterization module, the decay equation of the personalized pharmacokinetic model is: Wherein P (t) is the plasma concentration response of the unit dose of the rimazolam, t is time, A j and lambda i are both pharmacokinetic model parameters, s is the decay time length; In the plasma concentration response characterization module, the drug change rates of the central chamber, the first peripheral chamber and the second peripheral chamber in the personalized pharmacokinetic model are expressed by differential equations: Where X 1 (t)、X 2 (t)、X 3 (t) is the drug dose in the central chamber, the first peripheral chamber, and the second peripheral chamber at time period P i , respectively, k 10 、k 12 、k 13 is the drug elimination rate constant from the central chamber to the outside, from the central chamber to the first peripheral chamber, and from the central chamber to the second peripheral chamber, k 21 is the drug elimination rate constant from the first peripheral chamber to the central chamber, and k 31 is the drug infusion rate at time t for the drug elimination rate constant ;E 1 ＝k 12 +k 13 +k 10 ;E 2 ＝k 21 ;E 3 ＝k 31 ;I i (t) from the second peripheral chamber to the central chamber.
9. The system of claim 8, wherein the plasma drug concentration characterization module is configured to characterize the plasma drug concentration C p as a function of time: The state variable analysis module is characterized in that: The expression formula of the state variable R i (t) is: The time function characterized by plasma drug concentration is rewritten by state variable R i (t): The expression formula of the drug infusion quantity in the time t+delta t interval is as follows: Wherein P (t-t ') is the next dose change time interval, I represents a constant drug infusion rate, and I (t ') is the drug infusion rate at time t '.
10. The system of claim 9, wherein in the plasma drug concentration characterization module, the drug dosage expression formula for the central chamber, the first peripheral chamber, and the second peripheral chamber at time period P i is: Wherein X 1 (0)、X 2 (0)、X 3 (0) is the dose of period P i at time 0, lambda 1 、λ 2 、λ 3 is the three-exponential mixing rate constant of drug decay, k 0 is the zero-order infusion equation of period Pi drug, bi represents the single injection dose infusion of period Pi drug ;D 1 ＝(λ 2 -λ 1 )(λ 3 -λ 1 );D 2 ＝(λ 1 -λ 2 )(λ 3 -λ 2 );D 3 ＝(λ 1 -λ 2 )(λ 2 -λ 3 ); In the drug infusion rate calculation module, the plasma drug concentration at Δt time C p is calculated at rate=1 and initial R i (0) =0 before starting the control injection: At each iteration t+Δt, if there is no drug infusion, the plasma drug concentration C p (t+Δt) i＝0 at time t+2Δt is calculated: The drug injection rate I required from C p (t+Δt) to C T is: If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the desired C T .

Description

Rayleigh Malun target control infusion analysis method and system Technical Field The invention belongs to the technical field of target control infusion analysis, and particularly relates to a method and a system for target control infusion analysis of Rayleigh Malun. Background The target infusion (Target controlledinfusion, TCI) technology is a novel intravenous administration method for regulating and controlling the anesthesia depth by regulating the drug concentration of the plasma or an effect chamber based on the pharmacodynamic theory of medicine and based on the algorithm of the age, the sex, the weight and the height of a patient to calculate the concentration of the plasma and the effect part, so that the intravenous administration generates relatively stable and controllable plasma concentration. Compared with the traditional intravenous infusion technology, the target-controlled infusion can effectively reduce the fluctuation of circulation and respiration caused by the excessive change of the blood concentration, and maintain the anesthesia stability in the operation. At present, propofol TCI, etomidate TCI, remifentanil TCI, sufentanil TCI and the like are widely used clinically, and play a great role in anesthesia induction maintenance, different drugs have different pharmacokinetics and pharmacodynamics, and the target control infusion models of various drugs are different. Rayleigh Malun is a novel ultrashort-effect benzodiazepineThe medicine-like substance, rui Malun, has the characteristics of quick response, quick metabolism, short and constant continuous infusion half-life, low incidence rate of adverse reaction and the like, and is quite suitable for target controlled infusion in theory. In the prior art, the application mode of the rui Malun comprises single intravenous infusion and continuous pump infusion, has larger fluctuation of the blood concentration of the effect chamber of a patient, is unfavorable for maintaining stable circulation during anesthesia, and is easy to cause cardiovascular adverse events of the patient, and the safety is poor. The target control infusion system needs to be combined with the pharmacokinetics and pharmacodynamics individuation setting of different medicines, and the pharmacokinetics and pharmacodynamics parameters of the different medicines are different, so that the existing target control infusion system and model are not suitable for target control infusion of the Rayleigh Malun. It is necessary to develop a target controlled infusion analysis technical scheme of the Rayleigh Malun. Disclosure of Invention Therefore, the invention provides a method and a system for target control infusion analysis of a Rayleigh Malun, which solve the problems that the conventional technology is not suitable for target control infusion of a Rayleigh Malun, is difficult to maintain a stable blood concentration and has poor safety. In order to achieve the purpose, the invention provides the following technical scheme that the target control infusion analysis method for the Rayleigh Malun comprises the following steps: constructing an individualized pharmacokinetic model by adopting a three-chamber model, and characterizing the plasma concentration response of the unit dose Rayleigh Malun by the individualized pharmacokinetic model; Constructing an infusion pump control model, wherein the infusion pump control model characterizes the plasma drug concentration through a time function, and parameters of the time function comprise the index sum of the plasma concentration to unit dose Rayleigh (Malun) response determined by the individuation pharmacokinetics model; Defining a state variable R i (t) for the infusion pump control model, and calculating the state variable of the plasma drug concentration at the moment t+delta t according to the state variable of the plasma drug concentration at the moment t and the drug infusion quantity in the interval from the moment t to the moment t+delta t; The infusion pump control model utilizes the plasma drug concentration state variable at the current time t and the plasma drug concentration state variable at the time t+delta t to determine the drug infusion rate required by the plasma drug concentration to reach the target concentration CT. As a preferred embodiment of the target infusion analysis method of the rui Malun, the decay equation of the personalized pharmacokinetic model is as follows: Wherein P (t) is the plasma concentration response of the unit dose of the rimazolam, t is time, A j and lambda i are both pharmacokinetic model parameters, and s is the decay time length. As a preferred embodiment of the target-controlled infusion analysis method of the rui Malun, the drug change rates of the central chamber, the first peripheral chamber and the second peripheral chamber in the personalized pharmacokinetic model are expressed by differential equations: Where X 1(t)、X2(t)、X3 (t) is the drug dose in the central chamb