Acetaprofen

back pain,

joint pain,

muscle and rheumatic pain,

neuralgia,

headache,

migraine,

toothache,

painful menstruation,

sore throat,

feverish condition,

cold and flu symptoms,

symptomatic treatment of pain that requires a more pronounced analgesic effect than the effect of ibuprofen or paracetamol alone.

symptomatic therapy of infectious and inflammatory diseases (colds, flu), accompanied by fever, chills, headache, muscle and joint pain, sore throat,

myalgia,

neuralgia,

back pain,

joint pain, pain syndrome in inflammatory and degenerative diseases of the musculoskeletal system,

pain from bruises, sprains, dislocations, fractures,

post-traumatic and postoperative pain syndrome,

toothache,

algodismenorrhea (painful menstruation).

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

headache (including migraine),

toothache,

algodismenorrhea (painful menstruation),

neuralgia,

myalgia (muscle pain),

back pain,

joint pain, pain syndrome in inflammatory and regenerative diseases of the musculoskeletal system,

pain from bruises, sprains, dislocations, fractures,

post-traumatic and postoperative pain syndrome,

feverish states (fever).

The drug is used as a symptomatic treatment of acute respiratory diseases (colds) and flu: fever (fever), headache, muscle pain. The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

It is used in children from 3 to 12 years old:

febrile syndrome,

pain syndrome of various etiologies: toothache, sprains, dislocations, fractures,

as an auxiliary drug: tonsillitis, acute infectious and inflammatory diseases of the upper respiratory tract (pharyngitis, tracheitis, laryngitis).

It is used in children from 3 to 12 years old:

febrile syndrome,

pain syndrome of various etiologies: toothache, sprains, dislocations, fractures,

as an auxiliary drug: tonsillitis, acute infectious and inflammatory diseases of the upper respiratory tract (pharyngitis, tracheitis, laryngitis).

For adults:

moderate intensity pain syndrome in tramways (bruises, sprains, dislocations, fractures),

postoperative period,

algodismenorrhea,

toothache,

neuralgia,

myalgia,

lumbago,

fibrositis,

tendovaginitis,

rheumatoid arthritis,

osteoarthritis,

ankylosing spondylitis,

sinusitis,

tonsillitis,

headache,

fever.

For children (as an auxiliary tool):

tonsillitis,

acute infectious and inflammatory diseases of the upper respiratory tract.

Ibuprofen: absorption is high, quickly and almost completely absorbed from the gastrointestinal tract. The binding to plasma proteins is 90%. Slowly penetrates into the joint cavity, lingers in the synovial fluid, creating greater concentrations in it than in the blood plasma. It is detected in the blood plasma 5 minutes after taking the drug on an empty stomach, C_max in the blood plasma, it is reached after 1-2 hours. Simultaneous intake with food can reduce the concentration of ibuprofen in the blood plasma and increase the T_max. The degree of absorption of ibuprofen does not depend on the food intake. Undergoes metabolism in the liver. After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into the active S-form. T_1/2 — 2 h. It is excreted by the kidneys mainly in the form of metabolites (in unchanged form no more than 1%) and to a lesser extent-with bile in the form of metabolites. In older adults, there are no significant differences in the pharmacokinetic profile of ibuprofen compared to younger people. There is evidence that ibuprofen is found in breast milk in low concentrations.

Paracetamol: absorption is high, quickly absorbed from the gastrointestinal tract. The relationship with plasma proteins is insignificant when taken in therapeutic doses, slightly increases with overdose. It is detected in the blood plasma 5 minutes after taking the drug on an empty stomach, C_max the blood plasma level is reached in 30-40 minutes after administration. Concomitant intake with food may reduce the concentration of paracetamol in the blood plasma and increase the T_max. The degree of absorption of paracetamol does not depend on food intake. It is metabolized in the liver and excreted mainly in the form of glucuronides and sulfated conjugates to form glutathione conjugates (about 10%). It is excreted by the kidneys. In the form of unchanged paracetamol, less than 5% of the dose is excreted. T_1/2 - 3 h. The hydroxylated metabolite N-acetyl-p-benzoquinonimine, which is formed in small amounts in the liver and kidneys under the influence of mixed oxidases and is usually detoxified by binding to glutathione, can accumulate with an overdose of paracetamol and cause damage to liver tissue. In older adults, there are no significant differences in the pharmacokinetic profile of paracetamol compared to younger people.

The bioavailability and pharmacokinetic parameters of ibuprofen and paracetamol taken as part of this combined drug do not change either with a single or repeated use.

Ibuprofen

Absorption — high, quickly and almost completely absorbed from the gastrointestinal tract. T_max after oral administration-about 1-2 hours. The connection with plasma proteins is more than 90%. T_1/2 - about 2 hours. Slowly penetrates into the joint cavity, accumulates in the synovial fluid, creating higher concentrations in it than in the blood plasma. After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into the active S-form. Undergoes metabolism. More than 90% is excreted by the kidneys (in unchanged form, no more than 1%) and to a lesser extent with bile in the form of metabolites and their conjugates.

Paracetamol

The absorption is high, the binding to plasma proteins is less than 10% and increases slightly with overdose. The sulfate and glucuronide metabolites do not bind to plasma proteins, even at relatively high concentrations. The Value Of C_max — 5-20 mcg / ml, T_max - 0.5-2 hours. It is fairly evenly distributed in the liquid media of the body. Penetrates through the BBB.

About 90-95% of paracetamol is metabolized in the liver to form inactive conjugates with glucuronic acid (60%), taurine (35%) and cysteine (3%), as well as a small amount of hydroxylated and deacetylated metabolites. A small portion of the drug is hydroxylated by microsomal enzymes to form the highly active N-acetyl-n-benzoquinonimine, which binds to the sulfhydryl groups of glutathione. With depletion of glutathione reserves in the liver (in case of overdose), the enzyme systems of hepatocytes can be blocked, leading to the development of their necrosis.

T_1/2 - 2-3 hours — In patients with cirrhosis of the liver T_1/2 increases slightly. In elderly patients, the clearance of the drug decreases and the T increases_1/2. It is excreted by the kidneys, mainly in the form of glucuronide and sulfate conjugates (less than 5% - in unchanged form). Less than 1% of the taken dose of paracetamol penetrates into breast milk. In children, the ability to form conjugates with glucuronic acid is lower than in adults.

Ibuprofen. The absorption is slightly reduced when taking the drug after a meal. T_max when taken on an empty stomach-45 minutes, when taken after a meal-1.5-2.5 hours, in the synovial fluid-2-3 hours (the concentration of ibuprofen is higher than in blood plasma).

The binding to plasma proteins is 90%. Postischemia and undergoes first-pass metabolism in the liver. After absorption, about 60% of the pharmacologically inactive R-form of ibuprofen is slowly transformed into the active S-form.

The cytochrome P450 isoenzyme CYP2C9 participates in the metabolism of the drug. It has a two-phase elimination kinetics with T_1/2 2-2. 5 hours.

It is excreted by the kidneys (in unchanged form no more than 1%) and to a lesser extent-with bile.

Paracetamol. Absorption — high. T_1/2 it is reached in 0.5-2 h. C_max in blood plasma — 5-20 mcg/ml. Binding to plasma proteins-15%. Penetrates through the BBB. Less than 1% of the dose of paracetamol taken by a nursing mother enters breast milk. The therapeutically effective concentration of paracetamol in the plasma is achieved when it is administered at a dose of 10-15 mg/kg. It is metabolized in the liver (90-95%): 80% enters into conjugation reactions with glucuronic acid and sulfates to form inactive metabolites, 17% undergoes hydroxylation to form 8 active metabolites, which conjugate with glutathione to form already inactive metabolites. With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The cytochrome P450 isoenzyme CYP2E1 is also involved in the metabolism of paracetamol. T_1/2 - 1-4 hours — It is excreted by the kidneys in the form of metabolites, only 3% in unchanged form. In elderly patients, the clearance of the drug decreases and the T increases_1/2.