Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Anthracyclines and related substances, ATC code: L01D B01.

Doxorubicin belongs to the group of anthracyclines and is a cytostatic antibiotic that has been isolated from cultures of Streptomyces peucetius var. caesius. It is now prepared semi-synthetically from daunorubicin. Doxorubicin is a strong tissue irritant.

The biological activity of doxorubicin is attributed to its DNA-binding property, which results in inhibition of the enzymatic system, vital for the DNA replication and the DNA transcription. The blocking of the cellular cycle seems to be maximal during S phase and mitosis, but inhibition has also been observed during other cell cycle phases.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

After intravenous administration, doxorubicin elimination is characterized by a tri-phasic elimination from plasma with a terminal half-life of approximately 30 hours. The distribution volume is approximately 25 L/kg. The degree of protein binding in plasma is approximately 70%.

Highest drug concentrations are attained in the lung, liver, spleen, kidney, heart, small intestine and bone marrow. Doxorubicin does not cross the blood-brain barrier.

Doxorubicin is rapidly metabolised, and the main metabolite is the less active 13-dihydroderivative doxorubicinol. Within five days approximately 5% is recovered in the urine, whilst 40-50% is excreted through the bile within 7 days. Reduced liver function results in a slower elimination of the substance.