| Indication |
For the treatment of Koposi's sarcome connected to AIDS. |
| Pharmacodynamics |
Doxorubicin is an antineoplastic in the anthracycline class.
General properties of drugs in this class include: interaction with DNA
in a variety of different ways including intercalation (squeezing
between the base pairs), DNA strand breakage and inhibition with the
enzyme topoisomerase II. Most of these compounds have been isolated from
natural sources and antibiotics. However, they lack the specificity of
the antimicrobial antibiotics and thus produce significant toxicity. The
anthracyclines are among the most important antitumor drugs available.
Doxorubicin is widely used for the treatment of several solid tumors
while daunorubicin and idarubicin are used exclusively for the treatment
of leukemia. Doxorubicin may also inhibit polymerase activity, affect
regulation of gene expression, and produce free radical damage to DNA.
Doxorubicin possesses an antitumor effect against a wide spectrum of
tumors, either grafted or spontaneous. The anthracyclines are cell
cycle-nonspecific. |
| Mechanism of action |
Doxorubicin has antimitotic and cytotoxic activity through a
number of proposed mechanisms of action: Doxorubicin forms complexes
with DNA by intercalation between base pairs, and it inhibits
topoisomerase II activity by stabilizing the DNA-topoisomerase II
complex, preventing the religation portion of the ligation-religation
reaction that topoisomerase II catalyzes. |
| Absorption |
Not Available |
| Volume of distribution |
Not Available |
| Protein binding |
70% |
| Metabolism |
Not Available |
| Route of elimination |
Plasma clearance is in the range 324 to 809 mL/min/m2 and is predominately by metabolism and biliary excretion. |
| Half life |
55 hours |
| Clearance |
- 324-809 mL/min/m2
- 1088 mL/min/m2 [Men]
- 433 mL/min/m2 [Women]
- 1540 mL/min/m2 [children greater than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
- 813 mL/min/m2 [infants younger than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
|
| Toxicity |
LD50=21800 ug/kg (rat, subcutaneous) |
