Doxorubicin interaction

Doxorubicin interacts with molecular oxygen producing superoxide ions and hydrogen peroxide which cause single strand breaks in DNA. 

Paclitaxel also may be given concurrently with doxorubicin or epirubicin as a combination regimen. Pharmacokinetic interactions make these regimens more difficult to give. 

Capranico, G., Babudri, N., and Casciarii, G., 1986, Lack of effect of glutathione depletion on cytotoxicity, mutagenicity and DNA damage produced by doxorubicin in cultured cells. Chem.-Biol. Interact. 57 189-201... 

Aich P, Sen R, Dasgupta D (1992b) Role of magnesium ion in the interaction between chromomycin A3 and DNA binding of chromomycin A3 — Mg + complexes with DNA. Biochemistry 31 2988-2997 Akman SA, Doroshow JJH, Thomas G, Burke J, Dizdaroglus M (1992) DNA base modifications induced in isolated human chromatin by NADH de hydrogenase-catalyzed reduction of doxorubicin. Biochemistry, 31 3500-3506... 

Taquet A, Labarbe R, Houssier C (1998) Calorimetric investigation of ethidium and netropsin binding to chicken erythrocyte chromatin. Biochemistry 37(25) 9119—9126 Temple MD, McEadyen WD, Holmes RJ, Denny WA, Murray V (2000) Interaction of cisplatin and DNA-targeted 9-aminoacridine platinum complexes with DNA. Biochemistry 39(18) 5593-5599 Terasaki T, Iga T, Sugiyama Y, Hanano M (1984) Interaction of doxorubicin with nuclei isolated from rat liver and kidney. J Pharm Sci 73(4) 524—528... 

Zunino F, Di Marco A, Zaccara A, Gambetta RA (1980) The interaction of daunorubicin and doxorubicin with DNA and chromatin. Biochim Biophys Acta 607(2) 206-214... 

Drugs that may interact with stavudine include didanosine, doxorubicin, hydroxyurea, methadone, ribavirin, and zidovudine. 

Dexrazoxane (Zinecard) [Chelating Agent] Uses Prevent anthracycline-induced (eg, doxorubicin) cardiomyopathy Action Chelates heavy metals binds intracellular iron prevents anthracycline-induced free radicals Dose 10 1 ratio dexrazoxane doxorubicin 30 min prior to each dose, 5 1 ratio w/ CrCl <40 mL/min Caution [C, ] Contra Component sensitivity Disp Inj SE -1-BM (esp leukopenia), fever, Infxn, stomatitis, alopecia, NA /D Interactions t Length of muscle relaxation Wf succinylcholine EMS Given concurrent w/a chemo agent for treating CA to prevent cardiotox monitor for Infxn and reduced cardiac Fxn use caution w/ succinylcholine, reduced doses may be needed OD May cause extreme BM suppression symptomatic and supportive... 

Peg Interferon Alfa 2b (PEG-Intron) [Antiviral/ Immunomodulator] WARNING Can cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disord s. Monitor pts closely Uses Rx Hep C Action Immune modulation Dose 1 mcg/kg/wk SQ 1.5 mcg/kg/wk combined w/ ribavirin Caution [C, X if used w/ ribavirin /-] w/ Hx psychiatric Contra Autoimmune H, decompensated Uvct Dz, hemoglobinopathy Disp Vials 50, 80, 120, 150 mcg/0.5 mL Redipen 50, 80,120,150 mcg/5 mL reconstitute w/ 0.7 mL w/ sterile water SE D ession, insomnia, suicidal behavior, GI upset, neutropenia, thrombocytopenia, alopecia, pruritus Interactions t Myelosuppression W/ antineoplastics t effects OF doxorubicin, theophylline t neurotox W7 vinblastine EMS See Peg Interf on Alfa-2a may cause flu-like Sxs... 

Trastuzumab (Herceptin) [Antineeplastic/Monoover express the HERlIneu. protein breast CA adjuvant, w/ doxorubicin, cyclophosphamide, and paclitaxel if pt HER2/neu(+) Action MoAb binds human EGF receptor 2 protein HER2) mediates cellular cytotox Dose Per protocol, typical 2 mg/kg/IV/wk Caution [B, ] CV dysfxn, alla-gy/inf Rxns Contra Live vaccines Disp Inj SE Anemia, cardiomyopathy, nephrotic synd, pneumonitis Interactions t Risk of cardiac dysfxn W/ anthracycline, cyclophosphamide, doxorubicin, epirubicin EMS Cardiomyopathy, ventricular dysfxn and pulm tox have been reported monitor for Sxs of reduced cardiac Fxn OD Sxs unknown... 

In addition to the hydrophobic interaction mentioned above to encapsulate guest molecules, other types of nonspecific interactions have also been explored to enhance binding. For example, block copolymer micelles based on PEO as hydrophilic segments and poly(/3-benzyl L-aspartate) as hydrophobic blocks have used to encapsulate doxombicin. The encapsulation efficiency of doxombicin, an aromatic anticancer drug molecule, has been found to be significantly higher. This observation has been attributed to the tt-tt interaction between the anthracycUne moiety of doxorubicin and the benzyl group of poly(/3-benzyl L-aspartate) (Cammas-Marion et al. 1999). 

In addition to the intercalation mechanism described, the anthracycline ring of doxorubicin can undergo a one-electron reduction to form free radicals and participate in further electron transfer. These highly active substances can then react with tissue macromolecules. This type of interaction suggests an alternative mechanism of cytotoxicity for the anthracyclines. In particular, the cardiac toxicity of anthracyclines may result from the generation of free radicals of oxygen. 

Herceptin with cisplatin, doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel. A comparison of serum levels of trastuzumab given in combination with various chemotherapeutic agents did not suggest the possibility of any pharmacokinetic interactions except in combination with paclitaxel. Although not statistically signihcant, mean serum trough concentrations of trastuzumab were consistently elevated, about 1.5-fold, when Herceptin was administered in combination with paclitaxel. However, trastuzumab and paclitaxel were used concurrently in clinical trials with positive outcome results. The concurrent administration of anthracyclines, cyclophosphamide, and trastuzumab increased the incidence and severity of cardiac dysfunction during clinical trials. 

Similarly, green tea Camellia sinensis), a commonly consumed dietary supplement in many Asian countries, contains catechins, which have been shown to inhibit the activity of P-glycoprotein (26) and the efflux of doxorubicin by a carcinoma cell line (27). Although currently there is no literature report of an interaction between green tea and prescription or over-the-counter drug based on modulation of P-glycoprotein, a potential interaction between green tea and warfarin was reported and is described in Chapter 6. 

Non-covalent bonding includes hydrogen bonding, ionic bonds, or hydrophobic bonds. These types of bonding are involved in binding of chemicals to plasma proteins. They could also underlie the interaction between a chemical and a receptor or enzyme. Thus, the interaction between TCDD and the Ah receptor (AhR) and the intercalation of doxorubicin in DNA involve non-covalent bonds. 

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