First, the time-dose relationship and time-effect relationship of drugs
Time-dose relationship: the law of blood drug concentration changing with time.
Time-dose curve: blood samples were collected at different times after administration and plasma was separated. Through the education network of traditional Chinese medicine, the drug concentration in plasma was determined by appropriate collection and sorting methods. Taking time as the abscissa and blood concentration as the ordinate, curves reflecting the dynamic change of drug concentration in plasma are obtained, which are called blood concentration-time curve and real-time dose curve.
The change of blood drug concentration → reflecting the change of drug concentration at the site of action → the collection and arrangement of drugs should change with time.
Manifestation: The process from obvious efficacy to disappearance, and the relationship between efficacy and time becomes the prescription relationship of drugs.
Figure 2- 1 shows the blood concentration-time curve after a single oral administration, and the relationship between drug absorption, distribution and elimination is collected and sorted by the anti-drug education network.
The curve is divided into three stages:
Absorption and distribution stage: in the rising section of the curve, the drug is quickly absorbed from the drug-containing site and quickly distributed to the tissue, and the drug absorption is far greater than elimination.
Equilibrium period: in the middle of the curve, the drug absorption rate and elimination rate are similar, the drug concentration in the body reaches a temporary dynamic balance, and the change of blood drug concentration tends to be flat.
Elimination period: in the declining section of the curve, the blood drug concentration drops rapidly.
Area under curve (AUC): The area covered by medical education network under time-quantity curve, reflecting the total amount of drugs in blood. Significance: Reflect the degree of drug absorption. For the same subject, the higher the AUC, the higher the drug absorption.
The curve can be divided into three periods:
Incubation period: the time from administration to the beginning of curative effect. Reflect the absorption and distribution of drugs, but also related to the elimination of drugs.
Validity period: the time when drugs are collected and sorted to the lowest effective concentration by medical education network. The length depends on the absorption and elimination rate of drugs.
During this period:
There is a peak in blood drug concentration, which is called peak concentration. For a specific pharmaceutical preparation, the peak concentration is proportional to the dose.
The time required to reach the peak concentration is called peak time, and its length is related to the rate of absorption and elimination.
The sizes of C max and Tmax comprehensively reflect the absorption, distribution, excretion and metabolism of finishing agents collected by pharmaceutical education network. Cmax and Tmax of the same subject are mainly related to pharmaceutical preparations.
Residual period: the time when the blood concentration drops below the minimum effective concentration until it is completely eliminated from the body. The length depends on the elimination rate of drugs. Sleep drugs accumulate in the body for a long time, and repeated medication is easy to cause accumulation poisoning.
Second, the atrioventricular model
Car model: from the perspective of speed theory, establish a mathematical model to simulate the body. The whole body is regarded as a system, and then the system is divided into several atria according to its dynamic characteristics.
Atrioventricular:
(1) Abstract concept, which classifies tissues and organs with similar drug transport rates into a compartment. Does not represent a specific anatomical tissue or organ.
(2) In the same atrioventricular cavity, the dose of each tissue is not necessarily equal, and the transport rate between them is similar.
The transport and elimination of drugs in the body is a first-order process, so it is also called linear atrioventricular model, and its dynamic process is linear dynamics.
Common atrioventricular models are: one-compartment model and two-compartment model.
1. Single room model
One-room model: suppose that the corpse is collected and arranged by a medical education network consisting of three rooms. After intravenous administration, the drug can be quickly distributed in body fluids and tissues of the whole body, and the concentration of the drug in plasma and tissues can quickly reach a dynamic balance.
Intravenous administration: the curve of blood concentration c (logarithmic concentration)-time t is a single exponential function.
Calculation formula:
C=D/V e -kt=C0 e-kt
After a period of time, the blood concentration of C, the initial blood concentration of C o, the injection dose of D, the distribution volume of V = D/C0, the time of T, the elimination rate constant of K, and the base of the natural logarithm of E is 2.7 18.
Replace c = c o e-kt with ln (c/co) =-kt.
LnC plots time t to get a straight line with a slope of kω.
After the drugs treated according to the single-chamber model were collected by the Medical Education Network for intravenous administration, the plasma concentration (logarithmic concentration)-time curve was linear.
Because the time required to halve the blood concentration is called half-life (t 1/2), when C=0.5Co, t1/2 = ln 0.5/(-k) = 0.693/k. The visible half-life is inversely proportional to the elimination rate constant.
2. Two-compartment model
Two-compartment model: according to the different transport rates of drugs in tissues, the body is divided into central compartment and peripheral compartment.
Central ventricle: It is composed of some tissues with rich blood flow and good membrane permeability (such as heart, liver, lung, kidney, etc.). Distribution characteristics: drugs are easy to perfuse, and often enter such tissues first after entering the body. The medical education network can quickly collect and sort out the drugs in the blood stream and reach a balance with the drugs in these organizations.
Peripheral cavity: tissue that is difficult to perfuse (such as bone, fat, muscle at rest, etc.). Distribution characteristics: the drug transport rate is slow, and it takes some time for the drugs in the tissue and the drugs in the blood to reach a dynamic balance.
After intravenous injection of drugs, the plasma concentration (logarithmic concentration)-time curve presents a double exponential function.
Calculation formula:
C=Ae -αt+Be-βt
A and B are exponential coefficients, and α and β are distribution rate constants and elimination rate constants, respectively.
According to the two-compartment model, the semi-logarithmic plasma concentration-time curve is a double exponential curve, which is an important dynamic feature of the two-compartment model different from the single-compartment model.
The curve is divided into two stages:
After intravenous administration, the blood drug concentration is collected and sorted by medical education network, which is called distribution stage, mainly distribution.
Then it tends to be flat, mainly reflecting the elimination of drugs, which is called elimination period.