PHARMACOLOGY OF Topotecan (Hycamtin); Overview, pharmacokinetics, Mechanism of action, Uses, Effects скачать в хорошем качестве

PHARMACOLOGY OF Topotecan (Hycamtin); Overview, pharmacokinetics, Mechanism of action, Uses, Effects

Topotecan is a topoisomerase I inhibitor used primarily in the treatment of certain types of cancer, including ovarian cancer, small cell lung cancer, and cervical cancer. Here's an overview of its pharmacology: Mechanism of Action: Topoisomerase I Inhibition: Topotecan binds to the topoisomerase I-DNA complex, preventing the re-ligation of single-strand breaks induced by the enzyme. This leads to double-strand DNA breaks during DNA replication, which ultimately results in cell death2. Cytotoxicity: The cytotoxic effects of topotecan are due to the accumulation of double-strand DNA breaks, which mammalian cells cannot efficiently repair. Pharmacokinetics: Absorption: Topotecan is administered intravenously, and its pharmacokinetics are not influenced by food. Distribution: It is approximately 35% protein-bound and has a large volume of distribution. Metabolism: Topotecan undergoes reversible pH-dependent hydrolysis of its lactone moiety. It is metabolized to an N-demethylated metabolite in vitro2. Excretion: The drug and its metabolites are excreted in both urine and feces. Over 73% of the drug is recovered in urine and feces over 9 days2. Elimination Half-Life: The terminal half-life of topotecan is approximately 2 to 3 hours following intravenous administration. Clinical Use: Ovarian Cancer: Used for the treatment of advanced ovarian cancer in patients whose disease has recurred or progressed following platinum-based therapy. Small Cell Lung Cancer: Used as a second-line therapy for chemotherapy-sensitive small cell lung cancer. Cervical Cancer: Used in combination with cisplatin for the treatment of stage IVB, recurrent, or persistent cervical cancer. Side Effects: Common Side Effects: Bone marrow suppression, nausea, vomiting, diarrhea, and fatigue. Serious Side Effects: Severe neutropenia, thrombocytopenia, interstitial lung disease, and potential for severe hypersensitivity reactions #Topotecan