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Clearance Rate Pharmacokinetics

2021-03-05
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Pharmacokinetics is a branch of pharmacology, which provides a mathematical basis for evaluating the time course of drugs in the body and their effects. Pharmacokinetics can quantify the following processes: drug absorption, distribution, metabolism, and excretion. After the patient takes the drug, these pharmacokinetic processes (commonly called ADME) determine the concentration of the drug in the body. The effectiveness of drug treatment regimens depends on the concentration of the drug in the body. Therefore, it is necessary to have a basic understanding of the relevant pharmacokinetic parameters in order to design an appropriate drug treatment plan for the patient.
When analyzing pharmacokinetic data, nonlinear regression analysis is usually used for model fitting; or non-compartmental analysis (NCA) is used. The actual method used depends on the purpose of the data analysis. If the main purpose is to determine the exposure after drug administration (such as AUC), and drug-related pharmacokinetic parameters, such as clearance, terminal half-life, Tmax, Cmax, volume of distribution, etc., then NCA is usually the preferred method , Because it requires fewer assumptions than model-based methods. No matter which method is used, the above-mentioned drug-related pharmacokinetic parameters will be obtained. The key parameters include: drug clearance, terminal half-life, volume of distribution, bioavailability, etc.

Clearance Rate Pharmacokinetics

The plasma (total, system,…) clearance rate of a drug is determined by the clearance rate of all metabolic/elimination organs, which mainly involves the liver and kidney clearance of the drug. The plasma clearance rate (volume per time, or flow/flow) represents the overall ability of an animal or human individual to remove drugs from the body, and is scaled according to the corresponding plasma concentration of the drug (drug elimination rate, amount per time) To calculate. By calculating the overall body extraction ratio (value from 0 to 1), that is, the ratio of body clearance divided by cardiac output, the plasma clearance rate and its inter-species difference can be explained more easily. Compare. Plasma clearance is the most important pharmacokinetic parameter, because it is the only parameter that controls overall drug exposure (for a given bioavailability); it can also be used to calculate the average steady-state plasma for maintaining the drug Concentration required dose.

Plasma Clearance Rate

The plasma clearance rate of a drug is the most important of all pharmacokinetic (PK) parameters. Almost all PK papers report plasma clearance rates systematically, but they are rarely used in practice and are almost never seriously explained. This article aims to explain what is clearance rate, why plasma clearance rate is the most important PK parameter, how to calculate it, how to provide the physiological interpretation of its value in common animal species, and its main application in pharmacology.

Plasma clearance (CL) is the sum of the drug clearance rates of liver and kidney, that is, how much volume of plasma is cleared of drugs in a unit time, the unit is: L/h, for example, the unit of weight is L·kg /h.

Clinical Application

CL is the sum of the ability of liver and kidney to eliminate drugs, reflecting the body’s ability to eliminate drugs, and is closely related to the functional status of the body’s liver, kidneys and other organs that eliminate drugs. CL value when a certain body’s liver and (or) kidney function is poor Will decrease and affect the elimination of the drug. Generally speaking, poor liver function mainly affects the clearance rate of fat-soluble drugs; poor renal function mainly affects the clearance rate of water-soluble drugs. Clinically, drugs can be selected or adjusted appropriately based on the patient’s liver or kidney function status.

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