Paracetamol. Absorption is high. Connection with plasma proteins - 15%. Penetrates through the blood-brain barrier. Metabolised in the liver in three main ways: conjugation with glucuronides, conjugation with sulfates, oxidation with microsomal enzymes of the liver. In the latter case, toxic intermediate metabolites are formed, which are subsequently conjugated to glutathione, and then to cysteine and mercapturic acid.The main isoenzymes of cytochrome P450 for this pathway of metabolism are isoenzyme CYP2E1 (predominantly), CYP1A2 and CYP3A4 (a secondary role). With a deficiency of glutathione, these metabolites can cause damage and necrosis of hepatocytes. Additional metabolic pathways include hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol, which are subsequently conjugated to glucuronides or sulfates. In adults, glucuronation predominates. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity. It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% unchanged. In elderly patients, the clearance of the drug decreases and the half-life increases.
Based on the results of clinical studies, the following pharmacokinetic parameters of paracetamol are established: the maximum concentration in blood plasma is achieved by the application of capsules through 1.20 ± 0.72 hours and is 5.01 ± 1.70 μg / ml, the half-life is 3.04 ± 1.01 hours.
Ascorbic acid absorbed in the gastrointestinal tract (mainly in the jejunum). Connection with plasma proteins - 25%. Diseases of the gastrointestinal tract (peptic ulcer of stomach and duodenum, constipation or diarrhea, helminthic invasion, giardiasis), the use of fresh fruit and vegetable juices, alkaline drink reduce the absorption of ascorbic acid in the intestine. The concentration of ascorbic acid in the plasma is normally around 10-20 μg / ml. The time of maximum concentration in the blood plasma after ingestion is 4 hours. It easily penetrates into leukocytes, platelets, and then into all tissues; the greatest concentration is achieved in glandular organs, leukocytes, liver and lens of the eye; penetrates the placenta. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and in plasma. With deficient states, the concentration in leukocytes decreases later and more slowly and is considered as the best criterion for assessing the deficit than the concentration in the plasma. Metabolised mainly in the liver in desoxyascorbic and then in oxaloacetic acid and ascorbate-2-sulfate.It is excreted by the kidneys, through the intestine, with sweat in unchanged form and in the form of metabolites. Smoking and the use of ethanol accelerate the destruction of ascorbic acid (conversion into inactive metabolites), sharply reducing the reserves in the body. It is in hemodialysis.
Calcium gluconate. Approximately 1 / 5-1 / 3 part of the orally administered calcium gluconate is absorbed into the small intestine; this process depends on the presence of ergocalciferol, pH, dietary characteristics and the presence of factors capable of binding calcium ions. The absorption of calcium ions increases with its deficiency and the use of a diet with a reduced content of calcium ions. About 20% is excreted by the kidneys, the rest (80%) is the intestine.
Rimantadine. After oral administration, it is almost completely absorbed in the intestine. Absorption is slow. The connection with plasma proteins is about 40%. Scope distribution - 17-25 l / kg. The concentration in the nasal section is 50% higher than the plasma concentration. Metabolised in the liver. More than 90% is excreted by the kidneys within 72 hours, mainly in the form of metabolites, 15% - in unchanged form. In chronic renal failure, the elimination half-life is 2-fold.In individuals with kidney failure and in elderly people, it can accumulate in toxic concentrations if the dose is not adjusted in proportion to the decrease in creatinine clearance. Hemodialysis has an insignificant effect on the clearance of rimantadine.
Based on the results of clinical studies, the following pharmacokinetic parameters of rimantadine were established: the maximum concentration in blood plasma is achieved when the capsules are used after 4.53 ± 2.52 hours and is 68.2 ± 26.6 ng / ml, the elimination half-life is 30.51 ± 9, 83 hours
Rutozid. The time of maximum concentration in the blood plasma after ingestion is 1-9 hours. It is excreted mainly with bile and, to a lesser extent, kidneys. The half-life is 10-25 hours.
Loratadin. Quickly and completely absorbed in the gastrointestinal tract. The maximum concentration in the elderly is increased by 50%. The connection with plasma proteins is 97%. Metabolized in the liver with the formation of an active metabolite of descarbon ethoxyloratadine with the participation of cytochrome isoenzymes CYP3A4 and to a lesser extent CYP2D6. Does not penetrate the blood-brain barrier. It is excreted by the kidneys and with bile.In patients with chronic renal failure and during hemodialysis, the pharmacokinetics practically does not change.
The results of the clinical trials established the following pharmacokinetic parameters of loratadine: maximum plasma concentration is reached after 2.92 ± 1.31 hour and was 2.36 ± 1.53 ng / ml, half-life equal to 12.36 ± 6.84 h .