Daunorubicin pharmacokinetics

Daunorubicin is an anthracycline that is sometimes referred to as an antitumor antibiotic. Daunorubicin inserts between base pairs of DNA to cause structural changes in DNA however, the primary mechanism of cytotoxicity is the inhibition of topoisomerase II. The pharmacokinetics are best described by a two-compartment model, with a terminal half-life of about 20 hours. The predominant route of elimination of daunorubicin and hydroxylated metabolites is hepatobiliary... 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

Gill PS, Espina BM, Muggia F, Cabriales S, Tulpule A, Esplin JA, Liebman HA, Forssen E, Ross ME, Levine AM. Phase FII clinical and pharmacokinetic evaluation of liposomal daunorubicin. J Clin Oncol 1995 13(4) 996-1003. 

Paul C, Lliemark J, Tidefelt U, et al. Pharmacokinetics of daunorubicin and doxorubicin in plasma and leukemic-cell from patients with acute nonlymphoblastic leukemia. Drug Monit 1989 11 140-148. 

Pharmacokinetics Doxorubicin and daunorubicin must be given intravenously. They are metabolized in the liver, and the products are excreted in the bile and the urine (the red color is not hematuria). 

The citrate salt of daunorubicin is marketed as a liposomal formulation (Fig. 42.17), which promotes the use of this agent in solid tumors. Like Doxil (the liposomal formulation of doxorubicin), DaunoXome is indicated for use in AIDS-related Kaposi s sarcoma and is administered IV at a dose of 40 mg/m every 2 weeks. The pharmacokinetic profiles of Doxil and DaunoXome are similar. 

The pharmacokinetics, pharmacology, chemotherapeutic effects, toxicity, chromosome aberatlons and mutagenic potency of adriamycin were reported. 105-109 Adriamycin is useful for acute lymphoblastic and chronic myelogenous leukemias, transitional cell carcinoma, llposarcoma, squamous cell carcinoma, and adenocarcinoma of the breast. It is less toxic than daunorubicin. Resistance to daunorubicin is due to changes in the cellular membrane.no Both antibiotics possess Immunosuppressive properties.HI... 

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