Remazolam target control infusion analysis method and system
By constructing a three-compartment model of individualized pharmacokinetics and an infusion pump control model, the problem of blood drug concentration fluctuation in remimazolam target-controlled infusion was solved, achieving stable blood drug concentration control, reducing the risk of cardiovascular events, and providing a safe infusion protocol.
Patent Information
- Application Number
- CN202410370703.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-03-28
- Publication Date
- 2026-05-05
AI Technical Summary
Existing target-controlled infusion systems are not suitable for remimazolam, resulting in large fluctuations in blood drug concentrations during anesthesia, which increases the risk of adverse cardiovascular events in patients and has poor safety.
A three-compartment model was used to construct an individualized pharmacokinetic model. Plasma drug concentration was characterized by an infusion pump control model and a time function. The state variable Ri(t) was defined to calculate the drug infusion rate, thereby achieving precise control of plasma drug concentration.
This enables personalized dosing of remimazolam through target-controlled infusion, maintains stable blood drug concentrations, reduces the occurrence of adverse cardiovascular events in patients, and provides a comfortable and safe infusion protocol.
Smart Images
Figure CN121980980A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of target-controlled infusion analysis technology, specifically relating to a target-controlled infusion analysis method and system for remimazolam. Background Technology
[0002] Target-controlled infusion (TCI) is a novel intravenous drug delivery method based on pharmacokinetic theory. It uses algorithms to calculate plasma and effect site concentrations based on the patient's age, sex, weight, and height. By adjusting the drug concentration in the plasma or effect site, it regulates the depth of anesthesia, resulting in relatively stable and controllable plasma concentrations. Compared to traditional intravenous infusion techniques, TCI effectively reduces fluctuations in circulation and respiration caused by excessive changes in blood drug concentration, maintaining stable anesthesia during surgery. Currently, propofol TCI, etomidate TCI, remifentanil TCI, and sufentanil TCI are widely used clinically and have demonstrated significant advantages in anesthesia induction and maintenance. Different drugs have different pharmacokinetic and pharmacodynamic properties, and the target-controlled infusion models for each drug also vary.
[0003] Remimazolam is a novel ultra-short-acting benzodiazepine. Remimazolam, a drug of this class, is theoretically well-suited for target-controlled infusion due to its rapid onset of action, rapid metabolism, short and constant half-life with continuous infusion, and low incidence of adverse reactions. However, current technologies for remimazolam administration include single intravenous infusion and continuous infusion pump administration. These methods result in significant fluctuations in the patient's effect-site blood drug concentration, which is detrimental to maintaining circulatory stability during anesthesia and can easily lead to adverse cardiovascular events, resulting in poor safety. Target-controlled infusion systems require individualized settings based on the pharmacokinetic and pharmacodynamic parameters of different drugs. However, since different drugs have different pharmacokinetic and pharmacodynamic parameters, existing target-controlled infusion systems and models are not suitable for target-controlled infusion of remimazolam. Therefore, it is necessary to develop a target-controlled infusion analysis technique for remimazolam. Summary of the Invention
[0004] Therefore, this invention provides a target-controlled infusion analysis method and system for remimazolam, which solves the problems of traditional techniques being unsuitable for target-controlled infusion of remimazolam, making it difficult to maintain a relatively stable blood drug concentration, and resulting in poor safety.
[0005] To achieve the above objectives, the present invention provides the following technical solution: a remimazolam target-controlled infusion analysis method, comprising:
[0006] A three-compartment model was used to construct an individualized pharmacokinetic model, and the plasma concentration response of a unit dose of remimazolam was characterized by the individualized pharmacokinetic model.
[0007] An infusion pump control model is constructed, which characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam as determined by the individualized pharmacokinetic model.
[0008] Define a state variable R for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion amount in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt.
[0009] The infusion pump control model uses the plasma drug concentration state variables at the current time t and at time t+Δt to determine the drug infusion rate required to achieve the target plasma drug concentration CT.
[0010] As a preferred method for target-controlled infusion analysis of remimazolam, the decay equation of the individualized pharmacokinetic model is:
[0011]
[0012] In the formula, P(t) is the plasma concentration response at a unit dose of remimazolam, t is time, and A j and λ i All parameters are pharmacokinetic model parameters; s is the decay time length.
[0013] As a preferred method for target-controlled infusion analysis of remimazolam, the drug change rates in the central compartment, first peripheral compartment, and second peripheral compartment of the individualized pharmacokinetic model are expressed by differential equations as follows:
[0014]
[0015]
[0016]
[0017] In the formula, X1(t), X2(t), and X3(t) represent the values of X1(t), X2(t), and X3(t) respectively during time period P. i Drug dosage in the central chamber, first peripheral chamber, and second peripheral chamber; k 10 k 12 k 13 These are the drug elimination rate constants 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, respectively; k 21 k is the drug elimination rate constant from the first peripheral chamber to the central chamber. 31 E1 = k is the drug elimination rate constant from the second peripheral compartment to the central compartment. 12 +k 13 +k10 E2 = k 21 E3 = k 31 ;I i (t) represents the drug infusion rate at time t.
[0018] As a preferred method for target-controlled infusion analysis of remimazolam, plasma drug concentration C p The time function is represented as:
[0019]
[0020] State variable R i The formula for expressing (t) is:
[0021]
[0022] Through state variable R i (t) Rewrite the time function representing plasma drug concentration:
[0023]
[0024] The formula for expressing the drug infusion volume within the time interval t+Δt is:
[0025]
[0026] In the formula, P(t-t') is the time interval between the next dose change; I represents a constant drug infusion rate; and I(t') is the drug infusion rate at time t'.
[0027] As a preferred method for target-controlled infusion analysis of remimazolam, the central chamber, the first peripheral chamber, and the second peripheral chamber are in time period P. i The formula for expressing drug dosage at that time is:
[0028]
[0029]
[0030]
[0031] In the formula, X1(0), X2(0), and X3(0) are time periods P. i The dose at time 0; λ1, λ2, λ3 are the drug decay three-exponential mixing rate constants; k0 is the zero-order infusion equation of drug Pi for time period; Bi represents the single injection dose of drug Pi for time period; D1=(λ2-λ1)(λ3-λ1); D2=(λ1-λ2)(λ3-λ2); D3=(λ1-λ2)(λ2-λ3).
[0032] As a preferred method for target-controlled infusion analysis of remimazolam, before starting controlled injection, the rate = 1 and the initial R are calculated. i When (0) = 0, the plasma drug concentration C at time Δt. p :
[0033]
[0034] At each iteration t+Δt, if no drug infusion is performed, calculate the plasma drug concentration C at time t+2Δt. p (t+Δt) i＝0 :
[0035]
[0036] From C p (t+Δt) to C T The required drug injection rate I is:
[0037]
[0038] If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the required C. T .
[0039] This invention also provides a remimazolam target-controlled infusion analysis system, comprising:
[0040] The plasma concentration response characterization module is used to construct an individualized pharmacokinetic model using a three-compartment model, and to characterize the plasma concentration response of a unit dose of remimazolam through the individualized pharmacokinetic model;
[0041] A plasma drug concentration characterization module is used to construct an infusion pump control model, which characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam determined by the individualized pharmacokinetic model.
[0042] The state variable analysis module is used to define a state variable R for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion amount in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt.
[0043] The drug infusion rate calculation module is used by the infusion pump control model to determine the target concentration C of the plasma drug concentration at the current time t and the plasma drug concentration state variable at time t+Δt. T The required drug infusion rate.
[0044] As a preferred embodiment of the remimazolam target-controlled infusion analysis system, the decay equation of the individualized pharmacokinetic model in the plasma concentration response characterization module is as follows:
[0045]
[0046] In the formula, P(t) is the plasma concentration response at a unit dose of remimazolam, t is time, and A j and λ i All parameters are pharmacokinetic model parameters; s is the decay time.
[0047] In the plasma concentration response characterization module, the drug change rates in the central compartment, first peripheral compartment, and second peripheral compartment of the individualized pharmacokinetic model are expressed by differential equations as follows:
[0048]
[0049]
[0050]
[0051] In the formula, X1(t), X2(t), and X3(t) represent the values of X1(t), X2(t), and X3(t) respectively during time period P. i Drug dosage in the central chamber, first peripheral chamber, and second peripheral chamber; k 10 k 12 k 13 These are the drug elimination rate constants 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, respectively; k 21 k is the drug elimination rate constant from the first peripheral chamber to the central chamber. 31 E1 = k is the drug elimination rate constant from the second peripheral compartment to the central compartment. 12 +k 13 +k 10 E2 = k 21 E3 = k 31 ;I i (t) represents the drug infusion rate at time t.
[0052] As a preferred embodiment of the remimazolam target-controlled infusion analysis system, the plasma drug concentration characterization module includes a plasma drug concentration C. p The time function is represented as:
[0053]
[0054] In the state variable analysis module:
[0055] State variable R i The formula for expressing (t) is:
[0056]
[0057] Through state variable R i (t) Rewrite the time function representing plasma drug concentration:
[0058]
[0059] The formula for expressing the drug infusion volume within the time interval t+Δt is:
[0060]
[0061] In the formula, P(t-t') is the time interval between the next dose change; I represents a constant drug infusion rate; and I(t') is the drug infusion rate at time t'.
[0062] As a preferred embodiment of the remimazolam target-controlled infusion analysis system, the plasma drug concentration characterization module includes the central chamber, the first peripheral chamber, and the second peripheral chamber at time point P. i The formula for expressing drug dosage at that time is:
[0063]
[0064]
[0065]
[0066] In the formula, X1(0), X2(0), and X3(0) are time periods P. i The dose at time 0; λ1, λ2, λ3 are the drug decay three-exponential mixing rate constants; k0 is the zero-order infusion equation of drug Pi for time period; Bi represents the single injection dose of drug Pi for time period; D1=(λ2-λ1)(λ3-λ1); D2=(λ1-λ2)(λ3-λ2); D3=(λ1-λ2)(λ2-λ3);
[0067] In the drug infusion rate calculation module, before the controlled injection begins, the calculation rate is set to 1 and the initial R. i When (0) = 0, the plasma drug concentration C at time Δt. p :
[0068]
[0069] At each iteration t+Δt, if no drug infusion is performed, calculate the plasma drug concentration C at time t+2Δt. p (t+Δt) i =0:
[0070]
[0071] From Cp (t+Δt) to C T The required drug injection rate I is:
[0072]
[0073] If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the required C. T .
[0074] The beneficial effects of this invention are as follows: a three-compartment model is used to construct an individualized pharmacokinetic model, which characterizes the plasma concentration response to a unit dose of remimazolam; an infusion pump control model is constructed, which characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam determined by the individualized pharmacokinetic model; and a state variable R is defined for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion rate in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt; the infusion pump control model uses the plasma drug concentration state variables at the current time t and time t+Δt to determine the target concentration C of the plasma drug concentration. T The required drug infusion rate. This invention can rapidly achieve the blood drug concentration in the effect station by controlling the infusion pump, enabling individualized medication, maintaining a relatively stable blood drug concentration, reducing the occurrence of adverse cardiovascular events in patients, and providing patients with a comfortable and safe infusion protocol. Attached Figure Description
[0075] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are merely exemplary, and those skilled in the art can derive other embodiments based on the provided drawings without creative effort.
[0076] The structures, proportions, sizes, etc. illustrated in this specification are only for the purpose of assisting those skilled in the art in understanding and reading the content disclosed herein, and are not intended to limit the conditions under which the present invention can be implemented. Therefore, they have no substantial technical significance. Any modifications to the structure, changes in the proportions, or adjustments to the size, without affecting the effects and objectives that the present invention can produce, should still fall within the scope of the technical content disclosed in the present invention.
[0077] Figure 1This is a schematic diagram of the remimazolam target-controlled infusion analysis method provided in an embodiment of the present invention;
[0078] Figure 2 This is a schematic diagram illustrating the application of the remimazolam target-controlled infusion analysis method provided in this embodiment of the invention.
[0079] Figure 3 This is a schematic diagram of the remimazolam target-controlled infusion analysis system architecture provided in an embodiment of the present invention. Detailed Implementation
[0080] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0081] Example 1
[0082] See Figure 1 and Figure 2 The present invention provides a target-controlled infusion analysis method for remimazolam according to Embodiment 1, comprising the following steps:
[0083] S1. A three-compartment model is used to construct an individualized pharmacokinetic model, and the plasma concentration response of a unit dose of remimazolam is characterized by the individualized pharmacokinetic model.
[0084] S2. Construct an infusion pump control model, wherein the infusion pump control model characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam determined by the individualized pharmacokinetic model.
[0085] S3. Define a state variable R for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion amount in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt.
[0086] S4. The infusion pump control model uses the plasma drug concentration state variables at the current time t and at time t+Δt to determine when the plasma drug concentration reaches the target concentration C. T The required drug infusion rate.
[0087] In this embodiment, in step S1, a personalized pharmacokinetic model is established. Since remimazolam decay follows a three-compartment model, the decay equation of the personalized pharmacokinetic model is as follows:
[0088]
[0089] In the formula, P(t) is the plasma concentration response at a unit dose (kg / mL) of remimazolam, t is time, and A j and λ i All parameters are pharmacokinetic model parameters; s is the decay time length.
[0090] In the individualized pharmacokinetic model, the drug change rates in the central compartment, the first peripheral compartment, and the second peripheral compartment are expressed by differential equations as follows:
[0091]
[0092]
[0093]
[0094] In the formula, X1(t), X2(t), and X3(t) represent the values of X1(t), X2(t), and X3(t) respectively during time period P. i Drug dosage in the central chamber, first peripheral chamber, and second peripheral chamber; k 10 k 12 k 13 These are the drug elimination rate constants 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, respectively; k 21 k is the drug elimination rate constant from the first peripheral chamber to the central chamber. 31 E1 = k is the drug elimination rate constant from the second peripheral compartment to the central compartment. 12 +k 13 +k 10 E2 = k 21 E3 = k 31 ;I i (t) represents the drug infusion rate at time t.
[0095] In this embodiment, in step S2, the plasma drug concentration C p The time function is represented as
[0096]
[0097] P(t) describes the exponential sum of the response of plasma concentration to a unit dose, and a state variable R is defined. i (t), state variable R i The formula for expressing (t) is:
[0098]
[0099] Through state variable R i(t) Rewrite the time function representing plasma drug concentration:
[0100]
[0101] Because a state variable R is defined i (t), then:
[0102]
[0103] If the injection rate remains constant I during the time interval from t to t+Δt, the formula for the amount of drug infused during the time interval t+Δt is:
[0104]
[0105] In the formula, P(t-t') is the time interval between the next dose change; I represents a constant drug infusion rate; and I(t') is the drug infusion rate at time t'.
[0106] Among them, from R i(t) By definition, I can easily calculate R. i (t+Δt) is
[0107]
[0108] Therefore, the state variables at time t+Δt can be easily calculated from the state variables at time t and the infusion volume in the interval from t to t+Δt.
[0109] In this embodiment, the central room, the first peripheral room, and the second peripheral room are in time period P. i The formula for expressing drug dosage at that time is:
[0110]
[0111]
[0112]
[0113] In the formula, X1(0), X2(0), and X3(0) are time periods P. i The dose at time 0; λ1, λ2, λ3 are the drug decay three-exponential mixing rate constants; k0 is the zero-order infusion equation of drug Pi for time period; Bi represents the single injection dose of drug Pi for time period; D1=(λ2-λ1)(λ3-λ1); D2=(λ1-λ2)(λ3-λ2); D3=(λ1-λ2)(λ2-λ3).
[0114] In one possible embodiment, before starting controlled injection, the calculation rate = 1(C) is performed. p (Δt) i＝1) and initial R i When (0) = 0, the plasma drug concentration C at time Δt. p :
[0115]
[0116] In each iteration (time = t + Δt), if no drug infusion is performed, the plasma drug concentration C at time t + 2Δt is calculated. p (t+Δt) i＝0 :
[0117]
[0118] From C p (t+Δt) to C T The required drug injection rate I is:
[0119]
[0120] If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the required C. T .
[0121] Here, the calculation of I is merely an expression of the superposition principle for linear systems. C T -C p (t+2Δt) I＝0 This represents the distance between the target concentration and the predicted concentration at time t+2Δt. The infusion starting at time t+Δt will be added exactly to C. p (Δt) i＝1 To C p (t+2Δt) i＝0 The unit rate of an injection dose.
[0122] Therefore, C T -C p (t+Δ2t) i＝0 / C p (Δt) i＝1 This represents the number of unit rates within the time interval from t+Δt to t+2Δt, which is the infusion rate. C represents the number of units of rate within each time interval from t+Δt to t+2Δt. p (t+Δt) to C T Number of units required.
[0123] In summary, this invention employs a three-compartment model to construct a personalized pharmacokinetic model, which characterizes the plasma concentration response to a unit dose of remimazolam. An infusion pump control model is also constructed, which characterizes plasma drug concentration through a time function. The parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam determined by the personalized pharmacokinetic model. A state variable R is defined for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion rate in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt; the infusion pump control model uses the plasma drug concentration state variables at the current time t and time t+Δt to determine the target concentration C of the plasma drug concentration. T The required drug infusion rate. This invention can rapidly achieve the blood drug concentration in the effect room by controlling the infusion pump, enabling individualized medication, maintaining a relatively stable blood drug concentration, reducing the occurrence of adverse cardiovascular events during anesthesia induction and maintenance, and providing patients with a comfortable and safe infusion protocol.
[0124] It should be noted that the method of this disclosure embodiment can be executed by a single device, such as a computer or server. The method of this embodiment can also be applied to a distributed scenario, where multiple devices cooperate to complete the task. In such a distributed scenario, one of these devices may execute only one or more steps of the method of this disclosure embodiment, and the multiple devices will interact with each other to complete the method described.
[0125] It should be noted that the above description describes some embodiments of this disclosure. Other embodiments are within the scope of the appended claims. In some cases, the actions or steps recorded in the claims can be performed in a different order than that shown in the above embodiments and still achieve the desired result. Furthermore, the processes depicted in the drawings do not necessarily require a specific or sequential order to achieve the desired result. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.
[0126] Example 2
[0127] See Figure 3 Embodiment 2 of the present invention provides a remimazolam target-controlled infusion analysis system, comprising:
[0128] The plasma concentration response characterization module 001 is used to construct an individualized pharmacokinetic model using a three-compartment model, and to characterize the plasma concentration response of a unit dose of remimazolam through the individualized pharmacokinetic model.
[0129] The plasma drug concentration characterization module 002 is used to construct an infusion pump control model, which characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam determined by the individualized pharmacokinetic model.
[0130] State variable analysis module 003 is used to define a state variable R for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion amount in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt.
[0131] The drug infusion rate calculation module 004 is used by the infusion pump control model to determine the target concentration C of the plasma drug concentration when it reaches the specified time t, using the plasma drug concentration state variables at the current time t and at time t+Δt. T The required drug infusion rate.
[0132] In this embodiment, the decay equation of the individualized pharmacokinetic model in the plasma concentration response characterization module 001 is:
[0133]
[0134] In the formula, P(t) is the plasma concentration response at a unit dose of remimazolam, t is time, and A j and λ i All parameters are pharmacokinetic model parameters; s is the decay time.
[0135] In the plasma concentration response characterization module 001, the drug change rates in the central compartment, first peripheral compartment, and second peripheral compartment of the individualized pharmacokinetic model are expressed by differential equations as follows:
[0136]
[0137]
[0138]
[0139] In the formula, X1(t), X2(t), and X3(t) represent the values of X1(t), X2(t), and X3(t) respectively during time period P. i Drug dosage in the central chamber, first peripheral chamber, and second peripheral chamber; k 10 k 12 k 13 These are the drug elimination rate constants 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, respectively; k 21 k is the drug elimination rate constant from the first peripheral chamber to the central chamber.31 E1 = k is the drug elimination rate constant from the second peripheral compartment to the central compartment. 12 +k 13 +k 10 E2 = k 21 E3 = k 31 ;I i (t) represents the drug infusion rate at time t.
[0140] In this embodiment, in the plasma drug concentration characterization module 002, the plasma drug concentration C p The time function is represented as:
[0141]
[0142] In the state variable analysis module 003:
[0143] State variable R i The formula for expressing (t) is:
[0144]
[0145] Through state variable R i (t) Rewrite the time function representing plasma drug concentration:
[0146]
[0147] The formula for expressing the drug infusion volume within the time interval t+Δt is:
[0148]
[0149] In the formula, P(t-t') is the time interval between the next dose change; I represents a constant drug infusion rate; and I(t') is the drug infusion rate at time t'.
[0150] In this embodiment, in the plasma drug concentration characterization module 002, the central chamber, the first peripheral chamber, and the second peripheral chamber are in time period P. i The formula for expressing drug dosage at that time is:
[0151]
[0152]
[0153]
[0154] In the formula, X1(0), X2(0), and X3(0) are time periods P. iThe dose at time 0; λ1, λ2, λ3 are the drug decay three-exponential mixing rate constants; k0 is the zero-order infusion equation of drug Pi for time period; Bi represents the single injection dose of drug Pi for time period; D1=(λ2-λ1)(λ3-λ1); D2=(λ1-λ2)(λ3-λ2); D3=(λ1-λ2)(λ2-λ3);
[0155] In the drug infusion rate calculation module 004, before the controlled injection begins, the calculation rate = 1 and the initial R are set. i When (0) = 0, the plasma drug concentration C at time Δt. p :
[0156]
[0157] At each iteration t+Δt, if no drug infusion is performed, calculate the plasma drug concentration C at time t+2Δt. p (t+Δt) i＝0 :
[0158]
[0159] From C p (t+Δt) to C T The required drug injection rate I is:
[0160]
[0161] If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the required C. T .
[0162] It should be noted that the information interaction and execution process between the modules of the above system are based on the same concept as the method embodiment in Embodiment 1 of this application, and the resulting technical effects are the same as those in the method embodiment of this application. For details, please refer to the description in the method embodiment shown above in this application, and it will not be repeated here.
[0163] Example 3
[0164] Embodiment 3 of the present invention provides a non-transitory computer-readable storage medium storing program code for a remimazolam target-controlled infusion analysis method. The program code includes instructions for executing the remimazolam target-controlled infusion analysis method of Embodiment 1 or any possible implementation thereof.
[0165] Computer-readable storage media can be any available medium that a computer can access, or a data storage device such as a server or data center that integrates one or more available media. The available medium can be magnetic media (e.g., floppy disks, hard disks, magnetic tapes), optical media (e.g., DVDs), or semiconductor media (e.g., solid-state drives, SSDs).
[0166] Example 4
[0167] Embodiment 4 of the present invention provides an electronic device, including: a memory and a processor;
[0168] The processor and the memory communicate with each other via a bus; the memory stores program instructions that can be executed by the processor, and the processor can execute the remimazolam target-controlled infusion analysis method of Embodiment 1 or any possible implementation thereof by calling the program instructions.
[0169] Specifically, a processor can be implemented in hardware or software. When implemented in hardware, the processor can be a logic circuit, an integrated circuit, etc. When implemented in software, the processor can be a general-purpose processor that reads software code stored in memory. This memory can be integrated into the processor or located outside the processor and exist independently.
[0170] In the above embodiments, implementation can be achieved, in whole or in part, through software, hardware, firmware, or any combination thereof. When implemented in software, it can be implemented, in whole or in part, as a computer program product. The computer program product includes one or more computer instructions. When the computer program instructions are loaded and executed on a computer, all or part of the processes or functions described in the embodiments of the present invention are generated. The computer can be a general-purpose computer, a special-purpose computer, a computer network, or other programmable device. The computer instructions can be stored in a computer-readable storage medium or transmitted from one computer-readable storage medium to another. For example, the computer instructions can be transmitted from one website, computer, server, or data center to another website, computer, server, or data center via wired (e.g., coaxial cable, fiber optic, digital subscriber line (DSL)) or wireless (e.g., infrared, wireless, microwave, etc.) means.
[0171] It is obvious to those skilled in the art that the modules or steps of the present invention described above can be implemented using general-purpose computing devices. They can be centralized on a single computing device or distributed across a network of multiple computing devices. Optionally, they can be implemented using computer-executable program code, thereby storing them in a storage device for execution by a computing device. In some cases, the steps shown or described can be performed in a different order than those presented herein, or they can be fabricated as separate integrated circuit modules, or multiple modules or steps can be fabricated as a single integrated circuit module. Thus, the present invention is not limited to any particular combination of hardware and software.
[0172] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.
Claims
1. A method for analyzing target-controlled infusion of remimazolam, characterized in that, include: A three-compartment model was used to construct an individualized pharmacokinetic model, and the plasma concentration response of a unit dose of remimazolam was characterized by the individualized pharmacokinetic model. An infusion pump control model is constructed, which characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam as determined by the individualized pharmacokinetic model. Define a state variable R for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion amount in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt. The infusion pump control model uses the plasma drug concentration state variables at the current time t and at time t+Δt to determine when the plasma drug concentration reaches the target concentration C. T The required drug infusion rate.
2. The method for target-controlled infusion analysis of remimazolam according to claim 1, characterized in that, The decay equation of the individualized pharmacokinetic model is: In the formula, P(t) is the plasma concentration response at a unit dose of remimazolam, t is time, and A j and λ i All parameters are pharmacokinetic model parameters; s is the decay time length.
3. The method for target-controlled infusion analysis of remimazolam according to claim 2, characterized in that, The drug change rates in the central compartment, first peripheral compartment, and second peripheral compartment of the individualized pharmacokinetic model are expressed by differential equations as follows: In the formula, X1(t), X2(t), and X3(t) represent the values of X1(t), X2(t), and X3(t) respectively during time period P. i Drug dosage in the central chamber, first peripheral chamber, and second peripheral chamber; k 10 k 12 k 13 These are the drug elimination rate constants 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, respectively; k 21 k is the drug elimination rate constant from the first peripheral chamber to the central chamber. 31 E1 = k is the drug elimination rate constant from the second peripheral compartment to the central compartment. 12 +k 13 +k 10 E2 = k 21 E3 = k 31 ;I i (t) represents the drug infusion rate at time t.
4. The method for target-controlled infusion analysis of remimazolam according to claim 3, characterized in that, Plasma drug concentration C p The time function is represented as: State variable R i The formula for expressing (t) is: Through state variable R i (t) Rewrite the time function representing plasma drug concentration: The formula for expressing the drug infusion volume within the time interval t+Δt is: In the formula, P(t-t') is the time interval between the next dose change; I represents a constant drug infusion rate; and I(t') is the drug infusion rate at time t'.
5. The method for target-controlled infusion analysis of remimazolam according to claim 4, characterized in that, Central room, first perimeter room, and second perimeter room during time period P i The formula for expressing drug dosage at that time is: In the formula, X1(0), X2(0), and X3(0) are time periods P. i The dose at time 0; λ1, λ2, λ3 are the drug decay three-exponential mixing rate constants; k0 is the zero-order infusion equation of drug Pi for time period; Bi represents the single injection dose of drug Pi for time period; D1=(λ2-λ1)(λ3-λ1); D2=(λ1-λ2)(λ3-λ2); D3=(λ1-λ2)(λ2-λ3).
6. The method for target-controlled infusion analysis of remimazolam according to claim 5, characterized in that, Before starting controlled injection, calculate rate = 1 and initial R. i When (0) = 0, the plasma drug concentration C at time Δt. p : At each iteration t+Δt, if no drug infusion is performed, calculate the plasma drug concentration C at time t+2Δt. p (t+Δt) i＝0 : From C p (t+Δt) to C T The required drug injection rate I is: If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the required C. T .
7. A remimazolam target-controlled infusion analysis system, characterized in that, include: The plasma concentration response characterization module is used to construct an individualized pharmacokinetic model using a three-compartment model, and to characterize the plasma concentration response of a unit dose of remimazolam through the individualized pharmacokinetic model; A plasma drug concentration characterization module is used to construct an infusion pump control model, which characterizes plasma drug concentration through a time function; the parameters of the time function include the exponential sum of the plasma concentration response to a unit dose of remimazolam determined by the individualized pharmacokinetic model. The state variable analysis module is used to define a state variable R for the infusion pump control model. i (t), based on the plasma drug concentration state variable at the current time t and the drug infusion amount in the interval from the current time t to time t+Δt, calculate the plasma drug concentration state variable at time t+Δt. The drug infusion rate calculation module is used by the infusion pump control model to determine the target concentration C of the plasma drug concentration at the current time t and the plasma drug concentration state variable at time t+Δt. T The required drug infusion rate.
8. The remimazolam target-controlled infusion analysis system according to claim 7, characterized in that, In the plasma concentration response characterization module, the decay equation of the individualized pharmacokinetic model is: In the formula, P(t) is the plasma concentration response at a unit dose of remimazolam, t is time, and A j and λ i All parameters are pharmacokinetic model parameters; s is the decay time. In the plasma concentration response characterization module, the drug change rates in the central compartment, first peripheral compartment, and second peripheral compartment of the individualized pharmacokinetic model are expressed by differential equations as follows: In the formula, X1(t), X2(t), and X3(t) represent the values of X1(t), X2(t), and X3(t) respectively during time period P. i Drug dosage in the central chamber, first peripheral chamber, and second peripheral chamber; k 10 k 12 k 13 These are the drug elimination rate constants 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, respectively; k 21 k is the drug elimination rate constant from the first peripheral chamber to the central chamber. 31 E1 = k is the drug elimination rate constant from the second peripheral compartment to the central compartment. 12 +k 13 +k 10 E2 = k 21 E3 = k 31 ;I i (t) represents the drug infusion rate at time t.
9. The remimazolam target-controlled infusion analysis system according to claim 8, characterized in that, In the plasma drug concentration characterization module, the plasma drug concentration C p The time function is represented as: In the state variable analysis module: State variable R i The formula for expressing (t) is: Through state variable R i (t) Rewrite the time function representing plasma drug concentration: The formula for expressing the drug infusion volume within the time interval t+Δt is: In the formula, P(t-t') is the time interval between the next dose change; I represents a constant drug infusion rate; and I(t') is the drug infusion rate at time t'.
10. A remimazolam target-controlled infusion analysis system according to claim 9, characterized in that, In the plasma drug concentration characterization module, the central chamber, the first peripheral chamber, and the second peripheral chamber are in time period P. i The formula for expressing drug dosage at that time is: In the formula, X1(0), X2(0), and X3(0) are time periods P. i The dose at time 0; λ1, λ2, λ3 are the drug decay three-exponential mixing rate constants; k0 is the zero-order infusion equation of drug Pi for time period; Bi represents the single injection dose of drug Pi for time period; D1=(λ2-λ1)(λ3-λ1); D2=(λ1-λ2)(λ3-λ2); D3=(λ1-λ2)(λ2-λ3); In the drug infusion rate calculation module, before the controlled injection begins, the calculation rate is set to 1 and the initial R. i When (0) = 0, the plasma drug concentration C at time Δt. p : At each iteration t+Δt, if no drug infusion is performed, calculate the plasma drug concentration C at time t+2Δt. p (t+Δt) i＝0 : From C p (t+Δt) to C T The required drug injection rate I is: If I is less than 0, the drug infusion rate is 0 until the plasma drug concentration drops to the required C. T .