Because of the inhibitory effect of uracil , tegafur metabolite, increased in plasma. Pharmacokinetics After oral administration, the drug is rapidly absorbed. Maximum concentrations of tegafur, uracil and 5-fluorouracil -2 achieved after 1 hour. The presence of food with a high fat content, the index area under the curve “concentration-time» decrease in plasma and 37%, respectively, compared taking on an empty stomach. Tegafur plasma concentrations vary slightly. The values of maximum concentrations of tegafur, uracil reduced and time to achieve them increases. After oral administration, absorption and elimination of tegafur and uracil followed monoexponential kinetics. Tegafur Linking blood protein is 52%, the binding protein uracil blood negligible. Tegafur conversion to testosterone cypionate cycle prishodit (microsomal enzymes) and hydrolysis ‘(cytosolic enzymes). Microsomal oxidation of tegafur is partly isoenzyme cytochrome . Cytosol enzymes responsible for the metabolism of tegafur, remain unknown. The metabolism of occurs by way of natural degradation of the pyrimidine, uracil. Less than 20% of the drug is excreted in the urine in unchanged form. Half-life of tegafur and uracil after oral administration is 11 hours and 20-40 minutes, respectively.Three gidroksimetabolita tegafur are excreted in the urine.The concentration of uracil after the maximum concentration rapidly decreases. The maximum concentrations of are obtained in 30-60 minutes (approximately 200 ng / ml) and are determined at a concentration of more than 1 ng / ml for 8 hours before the next dose of the drug. noticeable accumulation of tegafur and uracil for 28 days of treatment was observed drug. The maximum concentration tegafur in blood plasma increases in proportion oral dose of 100 mg to 400 mg. The concentrations of uracil in the blood plasma increases more than proportionally to dose. Metabolism of the drug occurs mainly in the liver, therefore impaired renal function will have no significant effect on the pharmacokinetics.
Side effect From hemopoiesis system: the most severe is myelosuppression (anemia, leukopenia, thrombocytopenia). In very rare cases develop pancytopenia and agranulocytosis. From the nervous system: drowsiness, impaired consciousness, insomnia, depression, paresthesia, no smell, extrapyramidal disorders, urinary incontinence, paralysis. limbs, speech impairment, gait disturbance, dizziness, memory impairment, leukoencephalopathy. On the part of the gastrointestinal tract: nausea, stomatitis, dry mouth, anorexia, heartburn, vomiting, abdominal pain, constipation, flatulence, taste disorders, gastritis, gastric ulcers and / or duodenal ulcers. The most severe are diarrhea, hemorrhagic, ischemic or necrotic enteritis, acute pancreatitis, severe liver dysfunction, including fulminant hepatitis, cirrhosis of the liver. On the part of the respiratory system: interstitial pneumonia, cough. Cardio-vascular testosterone cypionate cycle system: angina, arrhythmia, ischemia and myocardial infarction. From the urinary system: acute renal failure, nephrotic syndrome, urinary incontinence, anuria, hematuria. skin and subcutaneous appendages: alopecia, exfoliative dermatitis (particularly sensitive palms and soles), violation of the pigmentation of the skin, rash, pruritus, urticaria , increased photosensitivity, discoid rash resembling systemic lupus erythematosus, nail changes structure.
In case of overdose, if the patient is conscious, induce vomiting or perform gastric lavage. It is necessary to establish strict control over the patient, and in particular the function of hematopoiesis and liver function tests. The specific antidote is unknown. Treatment is symptomatic.
Interaction with other medicinal products and other forms of interaction
Calcium folinate as biomodulyator, can enhance the antitumor effect of fluorouracil by stabilizing chelator and thymidylate due to the formation of intracellular metabolite 5,10-methylenetetrahydrofolate. Calcium folinate while taking did not significantly affect the pharmacokinetics of tegafur, uracil and 5 -ftoruratsila. Tegafur is partially metabolised by cytochrome testosterone cypionate cycle isoenzyme. Therefore, should be used with caution in combination with substrates or inhibitors of this enzyme – coumarin derivatives, metoksalenom, clotrimazole, ketoconazole, miconazole.
The simultaneous with drugs that suppress the enzyme is responsible for the catabolism of endogenous and fluorinated pyrimidines (such as brivudine) significantly enhances the toxicity .