Fluorouracil (fluorouracil) solution for injections 50 mg/ml. 5 ml. (250 mg.) №1

Description

Fluorouracil (fluorouracil) solution Storage:

active substance: fluorouracil;

1 ml of solution contains fluorouracil 50 mg;

Excipients: sodium hydroxide, water for injections.

Dosage form. Solution for injections.

Basic physical and chemical properties: transparent, colorless or almost colorless solution.

Fluorouracil (fluorouracil) solution Pharmacotherapeutic group.

Antineoplastic agents. Antimetabolites. Structural analogues of pyrimidine. ATX code L01B C02.

Fluorouracil (fluorouracil) solution Pharmacological properties.

Pharmacodynamics.

Fluorouracil is an analogue of uracil, a component of ribonucleic acid. It is believed that the drug functions as an antimetabolite. After intracellular conversion to the active deoxynucleotide, it inhibits DNA synthesis by blocking the conversion of deoxyuridic acid to thymidyl acid by the cellular enzyme thymidylate synthetase. Fluorouracil may also interfere with RNA synthesis.

Pharmacokinetics.

Absorption
After oral administration, fluorouracil is absorbed with very high variability in the gastrointestinal tract by first-pass metabolism caused by different levels of dihydropyrimidine dehydrogenase (DPD), the first enzyme for the catabolic conversion of fluorouracil.

Distribution
After intravenous fluorouracil is distributed in all body fluids and excreted from the blood within 3 hours. It is mainly absorbed by actively proliferating tissues and tumors after its conversion into a nucleotide. Fluorouracil easily passes through the blood-brain barrier and brain tissue.

Biotransformation
Dihydropyrimidine dehydrogenase is the initial enzyme of fluorouracil catabolism, which causes the catabolism of more than 85% of the administered dose to dihydrofluorourracil. Dihydrofluorouracil is then converted to fluoro-β-ureidopropionate and then to fluoro-β-alanine. Deficiency of enzymes in this process can lead to severe and even life-threatening toxicity of fluorouracil. In case of hepatic insufficiency, the metabolism of fluorouracil is slowed down, which may require dose adjustment.

Intracellularly, fluorouracil is converted to the active metabolites fluorodeoxyuridine monophosphate, fluorodeoxyuridine triphosphate and fluorouridine triphosphate by a number of enzymes.

Elimination
After intravenous administration, the half-life of fluorouracil in plasma is approximately 10-20 minutes and depends on the administered dose. After a single intravenous injection of fluorouracil, approximately 15% of the dose is excreted unchanged in the urine within 6 hours; more than 90% of the dose is excreted from the body within the first hour. The residue is metabolized mainly in the liver by the body’s normal mechanisms for uracil.

Clinical characteristics.

Indication.

Treatment of metastatic colorectal cancer;

adjuvant therapy for cancer of the colon and rectum;
treatment of advanced gastric cancer;
treatment of advanced pancreatic cancer;
treatment of advanced esophageal cancer;
treatment of advanced or metastatic breast cancer;
adjuvant therapy of operable primary invasive breast cancer;
treatment of inoperable locally advanced squamous cell carcinoma of the head and neck in previously untreated patients;
treatment of local recurrence or metastasis in squamous cell carcinoma of the head and neck.