Second-line therapy
Patients with advanced breast cancer who experience disease progression after first-line therapy may respond to subsequent chemotherapy regimens; however, response rates and durations are generally lower than those seen after initial treatment with these regimens (FEC and FAC). Dose escalation
A reduced dose intensity leads to reduced response rates . Equimolar doses of epirubicin and doxorubicin have been shown to be therapeutically equivalent in patients with metastatic breast cancer. Additionally the administration of more dose intensive epirubicin-containing regimens to patients with metastatic breast cancer has been associated with improved response rates, but not increased overall survival. It is suggested that it is necessary to at least double the dose of chemotherapy to detect a clinically relevant effect. Pharmacology
Mechanism of action
The mechanism of action of epirubicin is similar to that of doxorubicin and other anthracycline drugs. The observed clinical differences between epirubicin and doxorubicin can be explained by the pharmacokinetic differences based on the different affinity to DNA and lipophilicity, as there is no indication that different mechanisms are involved in their activity.Epirubicin first forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs. (Pharmacia & Upjohn Company LLC, 1999) This inhibits replication and transcription and triggers DNA cleavage by topoisomerase II. Epirubicin then stabilizes the topoisomerase II-DNA complex, resulting in irreversible DNA strand breakage, leading to cell death.
Once CBV-TP is integrated into the viral DNA, transcription and HIV reverse transcriptase is inhibited. Pharmacokinetics
Abacavir is given orally and is rapidly absorbed with a high bioavailability of 83%. Solution and tablet have comparable concentrations and bioavailability. Abacavir can be taken with or without food.Abacavir can cross the blood-brain barrier. Abacavir is metabolized primarily through the enzymes alcohol dehydrogenase and glucuronyl transferase to an inactive carboxylate and glucuronide metabolites. It has a half-life of approximately 1.5-2.0 hours. If a person has liver failure, abacavirs half life is increased by 58%.Abacavir is eliminated via excretion in the urine (83%) and feces (16%). It is unclear whether abacavir can be removed by hemodialysis or peritoneal dialysis. History
Robert Vince and Susan Daluge along with Mei Hua, a visiting scientist from China, developed the medication in the 80s.Abacavir was approved by the U.S. Food and Drug Administration (FDA) on 18 December 1998, and is thus the fifteenth approved antiretroviral drug in the United States. Its patent expired in the United States on 26 December 2009. Synthesis
References
Further reading
External links

"Abacavir". Drug Information Portal. U.S. National Library of Medicine. "Abacavir sulfate". Drug Information Portal. U.S. National Library of Medicine. Abacavir pathway on PharmGKB