In Vitro Drug Metabolism Models—Introduction and Main Applications of Microsomes

1 Drug Metabolism Sites
Drug metabolism sites are mainly divided into hepatic metabolism and extrahepatic metabolism
.


1.
1 Metabolism of drugs in the liver and its metabolic enzymes
The liver is the main metabolic organ of drugs, rich in phase I metabolic enzymes and phase II metabolic enzymes.
Most drugs are mainly biotransformed in the liver after entering the body, and are first metabolized in the first phase in the body.
Under the action of enzymes, it is oxidized, reduced and hydrolyzed, and then excreted in urine and feces with endogenous substances such as glucuronic acid or by methylation and acetylation under the action of phase II metabolic enzymes
.
Among the enzymes involved in drug metabolism in the liver, P450 enzymes are the most important and play a major role in drug metabolism
.


1.
2 The main sites of extrahepatic metabolism of drugs and their metabolizing enzymes The main sites of
extrahepatic metabolism of drugs include intestine, kidney and lung
.
Important drug-metabolizing enzymes in the gut are mainly distributed in epithelial cells, including CYP3A, glucuronyltransferase, and acetyltransferase
.
Drug metabolizing enzymes in the kidney are mainly distributed in the renal cortex and renal medulla, and phase II metabolism occupies a major position in renal metabolism
.
Drug metabolizing enzymes in the lungs mainly include P450 enzyme, hydrolase, monoamine oxidase, etc.
Among them, P450 enzyme plays an important role in the transformation of inhaled chemicals
.


2 In vitro drug metabolism model
2.
1 Overview of drug in vitro metabolism model
Drug metabolism research is divided into in vivo and in vitro research
.
Compared with in vivo metabolism research, in vitro metabolism research has certain advantages, which can reduce the interference of in vivo factors and directly observe the interaction process of drugs and enzymes, which has become a good research method for drug research and development
.
The main models of drug metabolism in vitro include gene recombinase, S9, cytosol, microsomes, primary cells,
etc.
Since the liver is the main site of drug metabolism, hepatocytes and their subcomponents such as liver microsomes, liver S9, and liver cytosol have become the main models for drug metabolism studies
.


2.
2 The main in vitro metabolism model of drugs—microsomes
2.
2.
1 Mainly used tissue microsomes and species
Liver microsomes exist in the endoplasmic reticulum and contain major drug metabolizing enzymes, such as CYP enzymes, flavin plus monooxygenase , carboxylesterase, glucuronyltransferase, etc.
, are responsible for 90% of drug metabolism reactions, and are the most widely used in vitro metabolic models
.
Oral drugs enter the body through the intestinal tract, and may be metabolized in the intestinal tract, thereby affecting the bioavailability of the drug.
Therefore, intestinal microsomes have also been widely used in the study of drug metabolism of oral preparations
.
There are relatively few types of pulmonary metabolic enzymes with low activity, but for topical preparations or sustained and controlled release preparations, they stay in the lungs for a long time, and it is generally believed that their metabolism in the lungs should be investigated.
Spread in lung microsomes or lung homogenates
.

The species of microsomes used for in vitro metabolism research of human chemical drugs mainly include humans, monkeys, dogs, rats, mice, hamsters, etc.
, and the species of veterinary chemical drugs mainly use microsomes of drug-using species, such as cattle sheep
etc.


2.
2.
2 Main applications of microsomes in drug metabolism in vitro The main applications of
microsomes in in vitro drug metabolism studies include species difference studies, metabolic stability studies, P450 inhibition studies, and metabolic phenotype studies.
These studies mainly use various species Multi-donor mixed microsomes
.
Genetic polymorphism studies mostly use single-donor microsomes
.


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Qi's Bio: Qi's Bio is committed to providing professional in vitro pharmacokinetic and toxicology testing systems
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.