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Anticancer Drugs Mitoxantrone Oncology Pharmacology Physiotherapy

Mitoxantrone (Mechanism of Action)

In this article we will discuss Mitoxantrone (Mechanism of Action)

In this article, we will discuss Mitoxantrone (Mechanism of Action). So, let’s get started.

Mechanism of Action

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen pre sentation, as well as the secretion of interferon gamma, TNFα, and IL-2.

Pharmacokinetics

Pharmacokinetics of mitoxantrone in patients following a single intravenous
administration of Mitoxantrone can be characterized by a three-compartment mode l. The mean alpha half-life of mitoxantrone is 6 to 12 minutes, the mean beta half-life is 1.1 to 3.1 hours and the mean gamma (terminal or elimination) half-life is 23 to 215 hours (median approximately 75 hours). Pharmacokinetic studies have not been performed in humans receiving multiple daily dosing. Distribution to tissues is extensive: steady-state volume of distribution exceeds 1,000 L/m². Tissue concentrations of mitoxantrone appear to exceed those in the blood during the terminal elimination phase. In the healthy monkey, distribution to brain, spinal cord, eye, and spinal fluid is low. In patients administered 15-90 mg/m² of Mitoxantrone intravenously, there is a linear relationship between dose and the area under the concentration-time curve (AUC). Mitoxantrone is 78% bound to plasma proteins in the observed concentration range of 26-455 ng/mL. This binding is independent of concentration and is not affected by the presence of phenytoin, doxorubicin, methotrexate, prednisone, prednisolone, heparin, or
aspirin.

Metabolism and Elimination

Mitoxantrone is excreted in urine and feces as either unchanged drug or as inactive metabolites. In human studies, 11% and 25% of the dose were recovere d in urine and feces, respectively, as either parent drug or metabolite during the 5-day period following drug administration. Of the material recovered in urine, 65% was unchanged drug. The remaining 35% was composed of monocarboxylic and dicarboxylic acid derivatives and
their glucuronide conjugates. The pathways leading to the metabolism of
Mitoxantrone have not been elucidated.

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