The impact of food on the absorption and pharmacokinetics of drugs

Food composition has a great influence on the absorption processes and drug metabolism, that appears to change their properties, the dynamics of binding with blood proteins, distribution and excretion of the body. Each of these steps is important, since the effect on the magnitude and duration of the therapeutic efficacy of drugs.

It should be noted that, Factors that, defining the processes of "suction" and "bioavailability" identical, but the results of drug efficacy when administered orally may vary materially. This is because, that a preparation with good absorption in the digestive tract can be subjected to intensive metabolism in the gut wall or hepatic first-pass, resulting in systemic circulation misses insignificant amount. For Example, pipolfen (Promethazine) It is well absorbed in the digestive tract (80% ), but its bioavailability is likely 25% as a result of metabolism in the liver at the first passage. There are other factors, affecting the effectiveness of drugs in general. For Example, taking into account the good solubility in lipids spironolactone, it should be administered after a meal. However, spironolactone reception simultaneously with food slows its absorption, but increases its bioavailability. Food slows the absorption gidralizina, but increases its bioavailability, resulting in a decrease in substance in the blood plasma after administration after meals, However, the hypotensive effect of increases, what to look for when appointing the drug. However, in most cases, concepts absorption and bioavailability were not significantly different. For Example, when decelerating under the influence of the absorbability of food amoxicillin, Ampicillin, acetylsalicylic acid, doxycycline, izoniazida, rifampicin, sulfalena, tetracycline, furosemida, Felodipine, cephalexin and other substances is reduced and the bioavailability of, and by increasing the absorbability of propranolol, gidralazina, gidroxlortiazida, griseofulvin, metoprolol, phenytoin - increased bioavailability.

Thus, in terms of clinical pharmacology drug interaction with food at step absorption in the gastrointestinal tract it is closely related to another pharmaco-kinetic exponent - bioavailability.

In the process of absorption affect the physicochemical properties of drugs (molecular size, solubility, stability, degree of ionization, etc.. d.); properties of drugs (Disintegration, the presence of auxiliary substances); they pass through the digestive tract; Numerous physiological factors of the patient (motor and secretory activity of the gastrointestinal tract, pH range, osmolality, suction machine status, its circulation and others.); content of the digestive tract, as well as the metabolism of drugs under the influence of bacterial microflora of guts; ability to chelate drugs- and complexes; the composition and viscosity of secretin; permeability of the digestive tract mucosa, etc.. Under the influence of qualitative and quantitative composition of food (sugar, amino acids, fat, fatty acids, glycerol, stearin, phytosterols, metal ion) changing solubility, absorption, metabolism and excretion of drugs.

Depending on the composition of the food has a different effect on the peristalsis and secretory function of the digestive tract, which affects the magnitude and rate of absorption of drugs. For Example, fats (especially those containing higher fatty acid) reduce the secretion of gastric juice, slow down the peristalsis of the stomach, which leads to a delay of digestive processes and mass transportation digestive. Under the influence of food, rich in fats, greatly reduced therapeutic efficacy of anthelmintic drugs, and nitrofurantoin, ʙenzonaftola, fenilsalitsilata. At the same time food, rich in fat, It can be useful in those cases, when it is necessary to increase the absorption of fat-soluble substances (antykoahulyantov, metronidazola, diazepama, vitamin A, D, E, K, griseofulvin, karʙamazepina, sulfonamides, and others.). Drug substances with high molecular weight (griseofulvin, spironolactone, nitrofurantoin) It is much better absorbed during a meal by increasing their solubility as a result of mixing in the stomach content and the presence of gastric juice, uniformly wetting all particles. Sugar also slow gastric emptying, resulting in delayed absorption sulphadimethoxin, sulfamethoxypyridazine and many other drugs.

Medicine, taken with meals, later into the intestine (principal place of suction), and therefore its effect comes later. Hence, when you want to get a quick therapeutic effect, take medication for 1 hours before or after meals 2 hours after eating the maximum particulate form, drinking 50-100 ml of boiled water.

The rate of passage of food through the stomach mass depends on the temperature. About 50% mass liquid pastry dishes at room temperature evacuated from the stomach through the 20-22 min., and after heating to 37 ° C - in 7 m.

Particular attention should be paid to intake of medicines and food, rich in protein. If the diet is dominated by whites, their number increases in blood, increases the degree of binding of the drug has grown deep albumin and globulins, which leads to a reduction of its therapeutic effectiveness. So, protein foods reduces the therapeutic effect of digitoxin, xinidina, cimetidine, caffeine, teofillina, tetracyclines, antykoahulyantov.

It was also established, that the ingestion of a high carbohydrate, fats or proteins tetracycline decreases the concentration in human serum at approximately 50%. In all these kinds of food below the maximum concentration of tetracycline, than when taking medications on an empty stomach.

Food components can adsorb drugs, envelop mucus, which also reduces their bioavailability.

Upon receipt of acetylsalicylic acid after eating its level in blood is halved compared with the administration on an empty stomach, Therefore, to achieve therapeutic concentrations of the drug must be assigned for 30 m. before meals. Simultaneous treatment with acetylsalicylic acid intake, rich in protein, fats or carbohydrates, reduces its concentration in the blood 50%. Traditional appointment of acetylsalicylic acid after a meal due to the fact, that it has a strong irritating effect on the gastric mucosa. To resolve this action is recommended to grind pills and drink water (1/3 cup) or starch mucus.

On the chemical structure (stability) drugs heavily influenced by the digestive juices, medium pH and enzymes. So, some drugs by the enzymes of the gastric mucosa may be subject to premature transformation (transformiruetsya levodopa into dopamine, Fosfestrol - into estrogens). These drugs should be as small as possible in the stomach. They are assigned primarily in the intervals between meals.

Medications have different efficiencies depending on, When adopted: during a meal or postprandial, due to a change in pH of the medium GI. So, Fasting and before eating slightly acid pH environment of the stomach. At this time, it should be low stabil- drug in an acidic medium (cardiac glycosides, geksametilentetramin), and preparations, does not irritate the digestive tract, based on their evacuation from the stomach during 1 no (before entering a food). Drug Absorption, taken on an empty stomach, usually, It is faster, because of their more complete contact with the surface of suction (GI mucosa). Medicine, taken on an empty stomach, after 10-15 m. can reach the intestine.

Between meals and thereafter reaches the acidic environment of the stomach pH 2,0-3,0, and the small intestine - 7,0-8,0. Such strongly acidic environment of the stomach and the alkaline environment of the intestine have a significant impact on the ionization and stability of drugs, their rate of passage through the digestive tract and absorption into the blood. So, eg, in the acidic environment partially inactivated benzylpenicillin, Erythromycin, lincomycin hydrochloride, oleandomiцin, cycloserine and other substances; Acetylsalicylic acid decomposes into its constituent parts - salicylic and acetic acid; hexamethylenetetramine - ammonia and formaldehyde; cardiac glycosides release aglycones.

Bile forms sparingly and nonabsorbable complexes with neomycin sulfate, polymyxin, Nystatin. Therefore, these drugs should be taken 40-60 m. before meals. Food reduces the absorption from the digestive canal penicillins, cephalosporins, slightly alter the absorption of doxycycline, amoxicillin and ampicillin.

Admission sulfonamides with food slows down its absorption. The metabolism of sulfonamides starting from the mucous membrane of the alimentary canal by acetylation, which leads to loss of their chemotherapeutic activity. So, sulfathiazole under the action of acidic gastric evacuation and slow in the stomach for acetylated 51%. In this regard, sulfonamides rationally take on an empty stomach, washing them down with alkaline solutions. For Example, sulfadimetoksin, passed for 40-60 m. before meals, absorbed much faster, than it received during the meal. Established, that when administered with food sulfadimetoksina its rate of absorption in the first 3-5 h reduced. In the appointment of sulfonamides therapeutic effect is expected in the first 2-3 h after administration, but this does not happen, if the drugs are taken just before eating or after.

Changing medium pH, and hence absorption of the drug, can occur when zapivaniya different fruit and berry juices, soft drinks and even milk.

The food changes the bioavailability of drugs with high first pass metabolic clearance. This is typical for lipophilic bases (propranolol, Amitriptyline) not typical for lipophilic acids (salicylic acid, penicillins), Although esters of such acids (acetylsalicylic acid, Pivampicillin) They are also subject to these processes. Food increases the bioavailability of spironolactone, dikumarina, b-адреноблокаторов.

In most cases, when prescribing medicines should be selected and an appropriate diet in order, the components of food did not alter the bioavailability of drugs and does not cause undesirable side effects.

In the treatment of Parkinson's disease should not eat beans, nuts and other products, soderzhaщie pyridoxine, which reduces the concentration of levodopa in the blood. Greens, containing vitamin K, Do not combine with anti-coagulant agents (derivatives of 4-hydroxycoumarin). When you receive a slowly absorbed drugs (digoxin and others.) should not be eaten plum jam, warm bread, dessert dishes, and laxatives, which accelerate peristalsis of the gastrointestinal tract. And when taking acetylsalicylic acid - food, rich in proteins, fats and carbohydrates, since the absorption of the substance is reduced 2 times, which leads to a reduction of its therapeutic effectiveness. Fish diet prolongs prothrombin time in patients, applying acetylsalicylic acid.

In the presence of folate in foods or benzoic acid significantly reduced or completely lost the therapeutic efficacy of sulfonamides. Latest, due to poor solubility, They may fall in the form of crystals in the kidney and break the mochevyvedeniya. To prevent this phenomenon patients when receiving sulfonamides (better on an empty stomach) You should get rich alkaline water (2-3 liters per day) in the form of alkaline mineral water or a solution of sodium hydrogencarbonate (0,5 teaspoon on 1 glass of water). With long-term appointment of sulfonamides (above 7 days) prophylactically can take vitamin food, soderzhaщuю thiamine, nicotinic, ascorbic acid, or preparation "Undevit". However, the interval between their methods should be at least 2 hours. It should be noted, that sulfonamides, cardiac glycosides and anticoagulant agents are of great affinity with protein, high content in chyme may constitute an obstacle to the achievement of the desired therapeutic effect. However, consider this a reason for contra-protein diets and vitamin inappropriate, since the processes of interaction between them can greatly reduce or negate by correcting the reception timing of medicines and food.

Vitamins (folic acid and vitamin B₁₂) appropriate diet and necessary in the case of diphenylhydantoin. They should be prescribed directly or through 1-2 hours after meals.

During medication, are secondary and tertiary amines (chlorpromazine, preparations, limiting appetite, biguanide antidiabetic, tetracikliny), do not eat sausages because of the possible formation of carcinogenic nitrosamines.

To prevent complications when taking corticosteroids and steroid hormones, causing changes in water-salt, protein, carbohydrate and fat metabolism, it is advisable to increase in your diet full of protein (cottage cheese, liver, lean meats, fish), potassium salts, Calcium, vitamins; reducing the number of easily digestible carbohydrates, fat, sodium chloride, sources of oxalic acid; the exclusion of refractory fats.

Treatment of many anticancer drugs requires enrichment diet food, improving hematopoiesis; Use of antimicrobials (antibiotics, TB drugs) - Complete vitamin diet; antykoahulyantov (neodikumarinov, phenyl ins and others.) - Increasing the sources of vitamins C and P simultaneously limiting green vegetables, containing vitamin K.

Treatment with hydrochlorothiazide, furosemide and other diuretics, causing an imbalance of potassium in the body, recommended by diet, rich in potassium salts, and with the appearance of symptoms of hypokalemia - taking drugs kalisodergaszczye (magnesium potassium aspartate and others.). Patients, were taking spironolactone, triamterene and amiloride, conversely, it is advisable to appoint a diet, poor potassium. Therapy and phenylbutazone salicylates can cause dyspepsia, stomach bleeding, therefore, need food, inflicting minimal chemical and mechanical effects on the stomach wall. The effectiveness of metronidazole increases against the backdrop of a conventional anti-ulcer diet.

Chronic administration of cholestyramine to lower cholesterol should be excluded from the diet of fatty meats, fish, fat, butter, cream, sour cream, and cholesterol-rich foods (egg yolks, liver, brains, kidneys). We need to eat more vegetables, fruit, as pectin and cellulose bind cholesterol in the intestine and promote its separation from the body.

Thus, appropriate nutritional therapy of medication should be considered as an additional, able to increase their efficiency and reduce the undesirable effects on the organism.

The nature of power has a significant effect on the metabolism of drugs. So, Vegetarians have reduced the rate of biotransformation of drugs. Individuals, Eat foods high in protein, rate of drug metabolism is increased.

When malnutrition or abuse its balance, protein deficiency a decrease in enzyme activity Multipurpose System oxidase in tissues, slowing elimination of drugs from the body, increasing the duration of their action (Pholcodine hydrochloride and others.). In the presence of large amounts of protein gastrointestinal therapeutic activity decreases cardiac glycosides, sulfonamides, antithrombotics. The simultaneous use of food, containing large amounts of tyramine and phenylethylamine (cheeses, cheese, cream, coffee, yeast, beer, risling wines and sherry), Serotonin (Pineapples, peanuts, bananas, nettle), dioksifeniletilamina (beans, beans, bananas) monoamine oxidase inhibitors (MAO) may lead to hypertensive crises. In the treatment of these complications hialamidom noted, Nonetheless, during his reception of these products is recommended to exclude from the diet. In some countries, the patient, The attending MAO inhibitors, handed a card with recommendations on diet and taking other medicines.

On the biotransformation of drugs has an effect and the lack of food proteins, fats and carbohydrates. This is particularly important in children: change rate of excretion of tetracycline, chloramphenicol; enhanced effect of phenobarbital and others., due, primarily, in violation of their metabolic processes. Similar patterns were found in adults in the study of the pharmacokinetics of doxycycline hydrochloride, rifampicin.

A pronounced effect on the metabolism of drugs has food, rich in vitamins, minerals, plant components. So, food, containing ascorbic acid, It stimulates the function oxidases, speeding up the metabolism of drugs, and in some cases reducing their toxicity. Food, containing folic acid, It speeds up the metabolism of diphenylhydantoin, vitamin B₆ reduces the effectiveness of levodopa. When nutritional deficiency of calcium and magnesium decreases oxidation paranitrobenzoynoy acid. Including in food spinach, white cabbage, containing large amounts of vitamin K, noticeable changes in prothrombin time, It stimulates the metabolism of oral anticoagulants, ʙarʙituratov, oxazepam. Reduction in plant food diet can improve the efficiency and anticoagulant therapy will reduce the dose of anticoagulant. The results of the interaction of certain foods and drugs are given in the tables above.

Thus, accumulated clinical data suggest, that drugs, with the exception of certain antibiotics and chemotherapy drugs (Isoniazid, rifampicin, tetracycline and penicillins with a narrow spectrum of activity), as well as such antidiabetic agents, as glibenclamide, drug glipizide and, It can be taken with food, since it reduces the irritant effect of drugs on the gastrointestinal mucosa and promotes more uniform their absorption into blood.

Some drugs and foods can change not only the pH environment of the stomach and intestine, but the pH of the urine, which depends on their tubular reabsorption. By adjusting via food urine pH, can weaken or strengthen the excretion of drugs. So, under alkaline conditions is enhanced urine excretion of sulfonamides, barbiturates, etc.. and, conversely, when acidic - slows.