Anthracycline drugs

Walker et al. (26) reported that doxorubicin, 2mg/mL in glass vials or plastic syringes and also 1 mg/mL in plastic syringes, is stable for 124 days when stored at 23°C without photoprotection. However, the photodegradation of anthracycline drug solutions (daunorubicin, doxorubicin, epirubicin) maybe substantial at concentrations below O.lmg/mL, if the solutions are exposed to UV-VIS radiation for longer periods (28,29). Above concentrations of 0.1 mg/mL, little or no photodegradation was observed. 

Griffiths GL, Mattes MJ, Stein R, et al. Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. Clin Cancer Res 2003 9 6567-65671. 

E) fluorescence emission of the anthracycline drug in a resistant-like environment and (F) fluorescence of the anthracycline drug in a sensitive-like environment. 

Lothstein L, Israel M, Sweatman TW. Anthracycline drug targeting cytoplasmic versus nuclear—a fork in the road. Drug Res Updates 2001 4 169-177. 

The level of formaldehyde above background in MCF-7 breast cancer cell lysates was a function of anthracycline drug concentration (0.5 - 50 pM), treatment time 3-24 h), cell density (03. x 10 to 7 X 10 cells per ml), and cell viability (0 - 100%) (Kato et al. 2000). Higher levels of formaldehyde were observed in lysates of MCF-7 cells treated at higher drug levels, unless the treatment resulted in low cell viability. 

Substituting EPI for DOX Lower formation of ROS or secondary alcohol metabolite Same as those of DOX combination with drugs that stimulate anthracycline conversion to secondary alcohol metabolite or diminish the cardiac defenses against ROS... 

DOX, as EPI seems to form fewer amounts of ROS and secondary alcohol metabolite, (ii) encapsulation of anthracyclines in uncoated or pegylated liposomes that ensure a good drug delivery to the tumor but not to the heart, (iii) conjugation of anthracyclines with chemical moieties that are selectively recognized by the tumor cells, (iv) coadministration of dexrazoxane, an iron chelator that diminishes the disturbances of iron metabolism and free radical formation in the heart, and (v) administration of anthracyclines by slow infusion rather than 5-10 min bolus (Table 1). Pharmacological interventions with antioxidants have also been considered, but the available clinical studies do not attest to an efficacy of this strategy. 

Each category of chemotherapy drugs has similar side effects. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. 

Clinicians should play a role in chemotherapy safety, patient education, and monitoring patient response to therapy. For example, cumulative doses of anthracyclines should be monitored along with signs and symptoms of heart failure. Clinicians also should monitor concurrent medications along with chemotherapy for drug interactions. 

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. 

Hyaluronidase is the antidote of choice for vinca alkaloid and high-concentration epipodophyllotoxin extravasations. Hyaluronidase breaks down hyaluronic acid, which functions as tissue cement. This promotes absorption of the extravasated drug away from the local site. Hyaluronidase also may be used for paclitaxel extravasations, but there are conflicting reports regarding its efficacy.39 Hyaluronidase should not be used with anthracycline extravasations because enhancement of local spread may occur. 

Heparin has been reported to complex with a variety of basic species, including biogenic amines and drugs for reviews, see Refs. 10 and 391. For its possible relevance to the pharmacological properties of heparin and complexed species, mention is made here of complexes with histamine392,393 and anthracycline antibiotics.394 C.d. studies on the interaction of basic homopolypeptides with heparin and other glycosaminogly-cans have shown that heparin is able to induce an ordered, helical conformation in the polypeptide.395 397 Similar, and even more dramatic, effects were observed with mixed basic polypeptides, presumed to represent better models for the biologically relevant interactions with plasma proteins.368... 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

There are various pathways for free radical-mediated processes in microsomes. Microsomes can stimulate free radical oxidation of various substrates through the formation of superoxide and hydroxyl radicals (the latter in the presence of iron) or by the direct interaction of chain electron carriers with these compounds. One-electron reduction of numerous electron acceptors has been extensively studied in connection with the conversion of quinone drugs and xenobiotics in microsomes into reactive semiquinones, capable of inducing damaging effects in humans. (In 1980s, the microsomal reduction of anticancer anthracycline antibiotics and related compounds were studied in detail due to possible mechanism of their cardiotoxic activity and was discussed by us earlier [37], It has been shown that semiquinones of... 

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