Geni cytochrome p450. Cytochrome P450 and pharmacokinetics of drugs. Cytochrome and metabolism of lycopene

cytochrome P450(CYP450) - a large group of enzymes, which are responsible for the metabolism of foreign organic spoluk and drug products. Enzymes of the cytochrome P450 family will help oxidize the biological transformation of drugs in a number of endogenous biological organisms and, in such a rank, detoxify the function. For the participation of cytochromes, the metabolism of the bacterial classes of lycars, such as proton pump inhibitors, antihistamines, retroviral protease inhibitors, benzodiazepines, calcium channel blockers, is attributed.

Cytochrome P450 is a complex of proteins with covalently bound heme (metaloprotein), which will prevent the transfer of acidity. Heme, in its turn, is a complex of protoporphyrin IX and a divalent atom of zaliz. The number 450 denotes that heme changes, dressings with CO, be the maximum of light weight at 450 nm.

Cytochrome P-450 plays a role not only in the metabolism of liquids, but also in the transformation of hemoglobin into bilirubin, synthesis of steroids and in the synthesis of steroids. All isoforms of cytochrome P-450 are combined into the CYP1, CYP2, CYP3 families. In the middle of families of images of pedrodynes A, B, C, D, E. In the boundaries of subfamilies the isoforms are designated by a serial number. For example, CYP2C19 is the name of the 19th cytochrome of the pedrodini "C", of the "2" family. In total, there are about 250 different types of cytochrome P-450, of which about 50 are in the human body and only a few of them (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4) may be metabolized before

The activity of cytochromes P-450 is infused with no factors - chicken, alcohol, alcohol, genetics, food, ailments. Tsi factors are responsible for the form individual features robotic enzymes R-450 and initiate the effective treatment of a particular patient.

The importance of cytochromes P450 for gastroenterology

Significantly increase in the remaining hours of interest in gastroenterologists to the isoforms of P450 CYP2C19 and CYP3A4 in their role in the metabolism of old benzimidazole, up to which all drugs are used for the preparation of ATSO from the pump2 group. Clinically, however, the CYP2C19 gene develops into a polymorphic gene in a patient, in the most significant world, the value of the therapeutic effect of the early IPP is found.

In the middle of the IPP, lansoprazole was most likely to develop CYP2C19, while omeprazole and esomeprazole were in the minority. It is also inferior to rabeprazole, which protects against the infusion on the activity of CYP2C19 on the basis of each of these substances, which is established in the course of non-enzymatic metabolism. Nadaє pantoprazole, who has been using the infusion on CYP2C19. The most inhibiting infusion on CYP3A4 in vitro in pantoprazole, dal (according to the change in effect) omeprazole, esomeprazole і rabeprazole і lansoprazole. For patients who dispense a small amount of drugs, the IPP is more potent than pantoprazole (Borin D.S.).

Metabolism of the five ingibitors of the proton pump.
More dark arrows mean more significant metabolism.
The little one takes from the statty Marelli S., Pace F.

The active participation of CYP3A4 is responsible for the metabolism of domperidone, cisapride and a great number of other types.

A number of gastroenterological preparations induce cytochrome CYP3A4, infusing them by themselves into the pharmacokinetics of accepted spirally.

The problem of interaction

In the current clinical practice, the combination of drug consumption is widely expanded, which is associated with the manifestation of a child's illness or the lack of effective monotherapy. With the combined therapy, interaction is possible. More than one person receives approximately 56% of patients under 65 years of age and 73% of patients over 65 years of age. Accept two ways to produce up to 6% of patients. Appreciating 5 (or 10) lіkіv increases the frequency of interactions up to 50 (or 100)%.

Potentially unsafe combination of leads is a serious key problem. From a date of 17 to 23% it is recognized as a combination of liquids and potentially not safe. Tilki in the United States through the non-transferable interaction of deaths 48 thousand ailments in the Rik. The FDA knew about the restoration of a number of leaks (including prokinetic cisaprides) through their potentially unsafe interactions with other leaks, which were brought, including to lethal inheritances.

The main mechanisms of interaction between changes are made between changes in pharmacokinetics and pharmacodynamics. Naybilsh іstotnymi, zgіdno happy news, Є changes in pharmacokinetics in the metabolism of liquids for the participation of cytochromes P-450.

With the help of not safe intercourse є recently the interconnection of the IPP and the clopidogrel has been discovered, it is widely stagnant in the case of illnesses on the ischemic ailment of the heart. To reduce the risk of gastrointestinal diseases, we are sick, as we take acetylsalicylic acid in a combination with clopidogrel, I mean IPP. Oscillations of bioactivation of clopidogrel are associated with the participation of CYP2C19, with IPP, metabolized by cytochrome, possibly reducing the activation and antiplatelet effect of clopidogrel. At the same time, 2009, at the conference of the Association of Heart Angiography and Inhabitation (SCAI), Bulls were presented with a date, but at once, a sick day was born, and an IPP signified a risk of death. D.Z.).

cytochrome CYP2C19

Isoform P450 CYP2C19 (S-mephenytoin hydroxylase) catalyzes the reaction of 5-hydroxylation of pyridine cycle and 5 "-demethylation in benzimidazole cycle.

All types of CYP2C19 mutations can be divided into three groups:

1. No mutations (homozygotes), stink and shvidky metabolizer IPP.
2. Tі, hto m mutation in one allele (heterozygote), an intermediate type of metabolism.
3. Ті, хто there are mutations in both alleles, the stench is the main metabolizer IPP.

Extensiveness of genotypes in CYP2C19, type of metabolism and effect of IPP in the presence of acid-acid diseases, the data in the tables are:

genotype CYP2C19	Expansion (Tkach S.M. ta in., 2006)			Metabolism type	The period of the IPP, T½, year (Lapina T.L.)	Acid-ingibuyuchiy effect IPP
		European race	Mongolian race
No mutations (homozygotes)	90% of the European population	50,6 %	34,0 %	Shvidky	1	low
Mutation in the 1st alei (heterozygote)	10% European population	40,5 %	47,6 %	industrial	-	middle
Mutations in both alleys	20-30% of the Asian population	3,3 %	18,4 %	povilny	2–10	high

Most metabolisers of both high and low levels are twice as high in concentration of IPP in blood plasma and periodically. The polymorphism of the gene, which is the code of the isoform 2C19, is responsible for the rapidity of the metabolism of the IPP in patients. It is recommended to carry out the control at the connection with the pidbir IPP additional pH meter(Khavkin A.I., Zhikhareva N.S., Drozdovskaya N.V.).

• CYP2C19 is extensively metabolized nastupnі Liky: tritsiklіchnіantidepresanti (amіtriptilіn, clomipramine, іmіpramіn), antidepressant - a selective іngіbіtor zvorotnogo zahoplennya serotonіnu citalopram antidepressant - іngіbіtor MAO moclobemide antіkonvulsіonnie i antіepelіptіcheskіe Costa (dіazepam, primіdon, fenіtoїn, fenobarbіtal, nordazepam) іngіbіtori protonnoї Pompey ( omeprazole, pantorazole, lansoprazole, rabeprazole and ezomeprazole), protimalarine proguanil, NPZP diclofenac and indomethacin, as well as: warfarin, gliclazide, clopidogrel, propranolol, cyclophosphosphamide,
• strong CYP2C19: moclobemide, fluvoxamin, chloramphenicol (levomycetin)
• nonspecific CYP2C19 Ingibitories: IPP omeprazole and lansoprazole, H2-blocker cimetidine, nonsteroidal anti-apical and indomethacin, as well as fluoxetine, felbamate, ketoconazole, modafinisil, oxcarinum
• Inductors CYP2C19: rifampicin, artemizinin, carbamazepin, norethisterone, prednizone, zombiy.

Infusion of different CYP2C19 genotypes on the effectiveness of Helicobacter pylori treatment

In patients with the genotype of "fast" metabolizers, the fast metabolism of the proton pump is indicated, and the antisecretory effect is the decrease in the rate of "phenotypes" of the "phenotypes" Riznitsya in the anti-secretory can make more low rіven eradication Helicobacter pylori in "quick" metabolizers. In such a rank, there is less and less efficiency of radiation therapy in patients with the genotypes of "grandparents" (88.9%) and "intermediate" (82.7%) metabolizers of food in the case of "young" (div. Malyunok).

Infusion of different CYP2C19 genotypes on the effectiveness of Helicobacter pylori treatment.
BM - "shvidki" metabolizators, PM - "industrial" metabolizators, MM - "povilny" metabolizators (Mayev І.V. and ін.)

Due to the fact that molecular-genetic advances are inaccessible to a practicing physician, it is possible to detect "fast" metabolizers to preserve abdominal pain on the 3-4th day when the ear is taken from the IPP, and until the endoscopic twisting defects in the patient. In my own way, the lack of antisecretory type of therapy due to IPP stasis can be verified by the method of additional internal drainage pH-meter (Mayev I.V. et al.).

cytochrome CYP3A4

The enzyme CYP3A4 catalyzes the reaction of sulfoxide, which leads to the approval of sulfogroup. CYP3A4 is one of the most important cytochromes for pharmaceuticals, since it is biotransformed, at least in a limited proportion, close to 60% of oxidized drugs. If the activity of CYP3A4 is widely varied, it is not strong to genetic polymorphism. The growth of CYP3A4 on the apical membranes of enterocytes of the small intestine and hepatocytes degrades the metabolism of liquids, so that speech is transferred to the systemic bloodstream, as it appears, as the "effect" of the first passage.

A genetic defect in CYP3A4 can be the cause of the development of secondary syndrome of the increased Q-T interval with the intake of cisapride і, as inherited, the development of the heart of Artim (Khavkin A.I. et al.).

• CYP3A4 Je basic enzyme at metabolіzmі the following lіkіv: іmunnodepressanti (cyclosporine, sirolіmus, takrolіmus) zasobi scho zastosovuyutsya at hіmіoterapії (anastrozole tsiklofosfamіd, docetaxel, erlotinіb, tіrfostіn, etopozid, ifosfamide, paklіtaksel tamoxifen, Tenіpozіd, vіnblastin, vіndezіn, gefіtinіb ), anti-fungal infections (clotrimazole, ketoconazole, іraconazole),

Cytochrome P450. Structure and function

The system P450 (P450 or CYP) in terms of catalytic activity and a great number of xenobiotics is among the enzymes of the 1st phase and the loan is carried out. The highest concentration of P450 appears in the EPR of hepatocytes (microsomes). The liver microsomal cytochrome P450 plays an important role in the specific intensity and hourly of foreign spores and the key - in the detoxification of xenobiotics, as well as in the activation of / pre-toxic cancer. P450-depleted monooxygenase - Multi-enzyme electronic transport system. All cytochromes P450 are heme-containing proteins. Consider the heme deposit in the oxidized state (Fe3 +). They are introduced to the Fe2 +, cytochrome P450 zdatny zv'yazuvati ligandi, such as kissen or monoxide in carbon. The complex, renewed to cytochrome P450 with CO, has a maximum of 450 nm, which has become a gift for

name tsikh enzymes. The main reaction, which catalyzes cytochrome P450, is monooxygenase, one atom is acidified in conjunction with the substrate (RH), and the latter is added to H2O. In the capacity of the lead in the reaction, the fate of NADPH:

RH (substrate) + O2 + NADPH + H + -> ROH (product) + H2O + NADP +

Mechanism, for which cytochrome will be removed from the electron from NADPH, to be deposited from the internal localization P450. In the EPR, a large number of hemoproteins are de-roted to take part in the biotransformation of xenobiotics, the electron is transmitted through flavoproteins, the title of NADPH-450 reductase. A single reductase molecule can deliver electricity to a small number of P450 molecules. In mitochondria, de-rosetting of itchroma P450, which take part in the biosynthesis of steroid hormones and metabolism of vitamin D, the electron is transferred with the help of two proteins: ferrodoxin and ferrodoxin-reductant.

In fig. 1 readings catalytic cycle P450. The first part is in the cycle of polarization in the activation of acid, the second - in the oxidized substrate. The scheme of the microsomal monooxygenase system was described by Estabruk z spivavt. The scheme is as follows: the first stage of the polyaga is at the interaction of the substrate with an oxidized form of 450. When P450 is involved with substrates

the transition of the hemogloss from the low-spine to the high-spine camp is changed. Another stage of the polyaga at the renewal, having adopted the enzyme-substrate complex with the first electron, which comes from the NADPH-specific lancet transferred from the NADPH through

flavoprotein I (NADPH-cytochrome P450 reductase). The third stage of polyaga in the context of the consumer complex: updates of P450-substrate-kisen. fourth stage

also updating the consumer complex with another electronic, yaky, yak

vvazhayut, come from the NADH-specific lance of the transfer of electrons, to store it from the NADN-

cytochrome b5 reductase abo flavoprotein II and cytochrome b5. The fifth stage is built up from decile processes, which include the internal molecular transformation of the new consumer complex and the solution of the hydroxylated product and water. At the third stage, cytochrome P450 transforms into an oxidized form.

Cytochrome P450 catalyzes offensive types of reactions: hydroxylation of an aliphatic or aromatic atom in carbon; epoxidation of the linkage;

oxidation of the atom (S, N, I) or N-hydroxylation; transfer of oxidized groups;

ruinuvannya etheric sound; dehydrogenation. Deyaki reactions, how to catalyze

cytochrome P450, shown in Fig. 2 and 3. Some of the reagent classes are good

hydroxylation remains in carbon in lancet, so called omega hydroxylation. So

Well, internal hydroxylation in decilkoh positions (positions -1, - 2).

It is necessary to produce up to no different types of products from such simple alkanes as hexane. Deliciously, cycling in carbohydrates can also undergo hydroxylation. In the reaction of hydroxylation, it is possible to establish itself on acetal, which then transforms into alcohol and aldehyde. When alkene is oxidized by cytochrome P450, diatomic oxide is established. Smells are perceived for their stability and may be very reactionary. For example, vinyl chloride is metabolically converted to oxide, which then converts to chloroacetaldehyde - a mutagen, which does not directly affect DNA. They brought them to the fence to the victorianna of vinilchloride in rospilyuvachi. Vinyl group of sterol (vinylbenzene), due to its carcinogenic power, alters the organism of humans and the state of the art, converting oxides into diol. Ale epoxіgіdrolase additional help is not expected. For example, cytochrome P450 synthesizes epoxide aflatoxin B1 in vivo. Tse z'єdnannya is a highly reactive electrofil, unstable and fast-form adduct with DNA. Until then, diol, which is established with epoxide, is itself unstable and highly reactive. Oxidation of aromatic spoluks with cytochrome P450 so it does epoxy, or even the stench quickly turn into phenol. As a result of hydroxylation of benzene, removal of phenol may be hydroxylated, passing into catechol or hydroquinone. Magnificently, catechol and hydroquinone can react with acidic, similar reactions with quinones, superoxides, and toxins. Also, at home, the formation of 2,3,7,8-tetrachloridebenzenedioxin (TCDD) is not strong before hydroxylation and is stable (the period of time in the organism of people is ric and more).

Microsomal oxidation - the end of reactions for participation oxygenaseі NADFN To produce a non-polar molecule before the atom is added to the storage of a non-polar molecule, it will show hydrophilicity and increase the response of the molecule ..

reactions microsomal oxidation to get rid of decilcom with enzymes, rosted on EPR membranes (in different in vitro the stench is called microsomal membranes). The enzymes organise short lantsyug, which end with cytochrome P 450.

Microsomal oxidation reactions before reaction phase 1 and the designation for the addition of hydrophobic molecules of polar powers, and / or for the improvement of the hydrophobicity, strengthening the reaction health of molecules for participation in the reactions of the second phase. The oxidation reactions are considered to be either hydroxyl, carboxyl, thiol and amino groups, and hydroxylic and hydroxylic groups.

Enzymes of microsomal oxidized growth in a smooth EPR і є oxidases with a change in function(Monooxygenase).

cytochrome P450

The main protein of microsomal oxidation of hemoproteins is cytochrome P 450. In nature, there are up to 150 isoforms of a protein, which oxidize about 3000 new substrates. The differentiation of different isoforms for cytochrome P450 grows due to genetic peculiarities. To get involved, one isoforms take part in the biological transformation of xenobiotics, and they metabolize endogenous spoluks (steroid hormones, prostaglandins, fatty acids, etc.).

cytochrome P450 in conjunction with molecular acidic and includes one atom of acidity in the molecule of the substrate, when it appears (becomes stronger) in its hydrophilicity, and the latter - in the molecule of water. The main yogo reactions є:

• oxidative dealkylation, which is supervised by oxidation of the alkyl group (at N, O or S atoms) to aldehyde and її by cleavage,
• oxidation (hydroxylation) of non-polar z'єdnan with aliphatic or aromatic rings,
• oxidation of alcohols to aldehyde aldehydes.

The robot cytochrome P 450 is provided with two enzymes:

• NADH-cytochrome b 5 -oxidoreductase, take revenge FAD,
• NADPH-cytochrome P 450 -oxidoreductase, take revenge FMNі FAD.

Scheme of reciprocal growth of microsomal oxidation enzymes and functions

Some oxidoreductases can be detected by electronics from some of the newer equivalents and transferred to the cytochrome P 450. The cytochrome blocks, in front of them, have received a molecule of the renewed substrate, ringing with the molecules. Having removed one more electron, cytochrome P 450 is included in the hydrophobic substrate of the first atom of acidity (oxidized to the substrate). Immediately I see the renewal of another atom to the point of water.

The sequence of reactions of hydroxylated substrates for the participation of cytochrome P450

Due to the peculiarity of microsomal oxidation є building up to induction or dropping, to change the process of exertion.

Inducers of speech, which activate the synthesis of cytochrome P 450 and transcription of related mRNAs. stink

1. wide range in other words, it may well stimulate the synthesis of cytochrome P 450, NADPH-cytochrome P 450 -oxidoreductase and glucuronyltransferase. A classic representative of є lost barbituric acid - barbіturati, also enter the qiu group diazepam, carbamazepin, rifampicin that in.

2. vuzkoy spectrum and diy, to stimulate one of the forms of cytochrome P 450 - aromatic polycyclic carbohydrates ( methylcholanthrene, spironolactone), Ethanol.

by the way, ethanol stimulates the synthesis of isoform P450 2E1 (alcohol oxidase) yak take the fate of metabolism, ethanol, nitrosamines, paracetamol and іn.
glucocorticoids Induce an isoform P 450 3A.

Ingibitories of microsomal oxidation are linked to the white part of the cytochrome or heme. Stink on:

1. werewolves

• directdiy- foul gas ( CO), antioxidant,
• indirectdiy, To infuse through the industrial products of their metabolism, as they set up complexes with cytochrome P 450 - erithromicine.

2. non-negotiableіngіbіtory - allopurinol, aminazine, progesterone, oral contraceptives, teturam, fluorouracil,

Assessment of reactions of the 1st phase

Assessment of microsomal oxidation can be carried out by the following methods:

• the value of the activity of enzymes in biopsies,
• from the pharmacokinetics of the drug,
• for additional metabolic markers ( antipyrine test).

antipyrine test

Obstezhuvaniy priymaє vrantsі natschesertse amidopyrine with a rozrahunku 6 mg / kg vagi. Get 4 portions of the section in the interval from 1 to 6 years, 6-12, 12-24 and 45-48 years. Obsyag sich vimіryuєtsya. Chi does not get worse, after 24 years the slaughter is centrifuged or filtered. The concentration of 4-aminoantipyrin and its metabolism of N-acetyl-4-aminoantipyrin in the cross section was further revealed.

Bilky of cytochrome P450 people are a great family of 56 different enzymes, which are encoded by different CYP genes. All P450 enzymes - heme-containing liver bricks; Fe + 2 in heme allows it to accept electrons from donors of electrons, for example, nikotinamidadeninucleotide phosphate (NADP), sirki.

At the time of the bagatokh of the lykarsky zasobiv pid for cytochromes P450 added to the hydroxyl group molecule. The whole process is called the first phase of the metabolism of liquids - the introduction of a larger polar group to the warehouse, which will provide easy access to the smaller group. hydroxyl group, Accepted in phase I, crossing the point of entry to liquids in a carbohydrate or acetyl group, to detoxify the lykar process and significantly reduce the appearance of liquor (phase II metabolism of liquids).

cytochrome P450 grouped into 20 families according to the homology of amino acid endings. Three families - CYP1, CYP2 and CYP3 replace enzymes that are not specific to substrates and take part in the metabolism of a large number of foreign speech (xenobiotics), including leaks. Particularly important for pharmacogenetics are the number of genes (CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4);

only CYP3A4 inclusions in the metabolism of 40% of all types of food, which can be used in clinical medicine. In addition, the rich CYP gene is even more polymorphic, with alleles, which may be real functional inheritance for the reaction to drug therapy. Alleles of CYP can produce up to the daytime, change or alter the activity of the enzyme, injecting into the metabolic rate of bagatokh lykarsky zasobiv. For example, CYP2D6 is the primary cytochrome in the first phase of metabolism, active more than 70 times for 70 years. There are described 26 alleles in the CYP2D6 gene, which can be added to its activity, reduced, absorbed or increased (block).

Missens mutations to decrease the activity of cytochrome cytochromes; alleles, for which the activity during the day is increased, is caused by mutations to splicing or to the frame. As for them, the CYP2D6 * 1XN allele is a series of copies of the numerical polymorphism of alleles, since the CYP2D gene is present in three, more or less copies in one chromosome. Yak and slid bulo ochikuvati, copies to produce to the high activity of the enzyme. There are more than a dozen alleles, which do not fit into the function of the library and are used as a wild type. The development of combinations of some of the classes of alleles should be produced up to the smallest indications of metabolic activity, in order to develop the combination of the combination even worse and lack of recovery. You can see three main phenotypes: normal, decreased and quick metabolism.

INDIVIDUUM ZI REDUCE metabolism there may be an obvious risk of accumulation of toxic rivnya lekiv. With a fast metabolism є a risk of lack of effect in case of vicious doses, inadequate for the preparation of a therapeutic dose of a drug in the blood.

snakes enzymes cytochrome P450 It is important not only for the detoxification of drugs, the stench can also take a part in the activation of drugs. For example, codeine is a weak drug, which will cause illness for the disease to be converted into morphine - an active metabolite in 10-fold change.

converting to the visonє enzyme CYP2D6... Individuals with a low metabolism, wicking the second active alleles in the CYP2D6 gene, do not convert codeine into morphine, so they take little therapeutic coryza. I, navpaki, for patients with increased metabolism of low doses of codeine can be toxic.

General and quick metabolism may be more accelerated, especially for the establishment of pharmacogenetics in personalized genetic medicine. The frequency of cytochrome P450 bagatech alelices is different in the older populations. For example, the phenotype with the general metabolism of CYP2D6 is present in 1 out of 14 Europeans, rarely occurs in Mongolians and is practically present in American Indians and Oceanic people. The analogous rank of the allele due to the general metabolism of the CYP2C19 gene may be different, varying from 3% in Europeans and up to 16% in all Mongoloids, which may have a general metabolism.

Cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9). Revealed mutation A1075C (Ile359Leu)

Gene name -CYP2C9

Localization of the gene on the chromosome- 10q23.33

• *1/*1
• *1/*3
• *3/*3

Population performance

allele CYP2C9 * 3 meet with Europeans with a frequency of 6%.

Association of the marker with the metabolism of drugs

Dosage for the development of physiological efficacy of drug intake: oral anticoagulants in the class of coumarin (warfarin), old sulfonylsecovin, non-narcotic analgesics (tenoxiprofen, flurroxin)

General information about the news

For the reduction and treatment of thromboembolic patients, the drug warfarin ("Coumadina") is often used. It is designated for trivial admission in a series of patients who are tied to the larynx of blood, as well as in the period of operative period with the method of getting a thrombus in the case of surgical intervention. Often practice the drug is used for people who have suffered an insult, myocardial infarction.

To achieve the effect of drugs, it is necessary to bioactivate organisms (transformation into an active form) in liver cells (hepatocytes) by the P450 enzyme system (CYP). Geni, who code for enzymes, polymorphs, and often aleles are heard, that code for the establishment of enzymes with a decrease in or out of the day function.

On the activity of cytochromes, in addition to the peculiarities of budov and coding of geni, such officials, such as vik, masa tila, way of life, great little calls, special features of children, adolescents, drug use, are added. These factors are responsible for the formulation of individual features of the robotic enzymes P450 and the nature of the metabolism of a greater degree. The head enzyme of biotransformation of indirect anticoagulants є isoenzyme to cytochrome P450 CYP2C9.

gene CYP2C9 localized on the 10th chromosome at distance 10q23.33. Find the options of the gene (aleli) CYP2C9, SCHO koduyut approval of the enzyme with a decrease in any day-to-day function. A variant of the gene that does not replace adenine for cytosine at position 1 075 (A1075C), leading to a decrease in the metabolic activity of the enzyme and CYP2C9 * 3. Thus, the enzyme is synthesized with a change in function, the activity of which becomes less than 5% of the activity of the enzyme * 1. The main (unchanged) variant of the gene is known as CYP2C9 * 1.

The most widening of the genotype, which zoom in on the normal metabolism of warfarin and start, such as CYP2C9 * 1 / * 1.

genetic marker CYP2C9 * 3(Genotypes * 3 / * 3 і * 3 / * 1) dressings due to the change in functional activity of the enzyme cytochrome P450, which reduces the efficiency of the administration of warfarin to the body. The presence of a patient alele * 3 to produce an overdose of the activity of the cytochrome isoenzyme, so that the anticoagulation effect of the drug is increased up to 7 times, and can serve as a reason for the development of such an accelerated blood flow, such as