Protein binding of anthraquinone glycosides, with special reference to adriamycin

Abstract

The binding of anthraquinone glycosides (adriamycin, adriamycinol, daunorubicin, daunorubicinol, and 4'epiadriamycin) to human serum albumin and human plasma has been studied by equilibrium dialysis. About 62% of adriamycin was bound to human serum albumin (45 g/l). Only minor variations in the degree of binding were observed between the anthraquinone glycosides. The binding degree of adriamycin in plasma from cancer patients was not significantly different from that observed in healthy volunteers, the fraction of free adriamycin being 24.56% +/- 4.51%, and 27.67% +/- 2.78%, respectively. The plasma albumin concentration was significantly lower in cancer patients than in the healthy volunteers (26.90% +/- 5.88% and 39.24% +/- 1.74%, respectively). In cancer patients the fraction of free adriamycin decreased with increasing plasma albumin concentration.

CE‐LIF method for the separation of anthracyclines: Application to protein binding analysis in plasma using ultrafiltration

“…Ultrafiltration was previously applied to the serum protein binding of these anthracyclines, binding values in the range of 56.9 -63.1% were obtained [15]. The protein binding results achieved in this study were also equivalent to those previously obtained by equilibrium dialysis [10,13,14]. As anthracyclines are highly protein bound, the volume of bound drug will be reduced.…”

“…For this work, the centrifugal speed and the duration of ultrafiltration employed corresponded to the guidelines specified by Fisher Scientific (47006g and 12 min). In a protein binding investigation of anthracyclines by Eksborg et al [14], it was determined that the degree of binding of DAN to albumin was independent of the initial drug concentration employed, and as a result it was assumed that the protein binding of the other anthracyclines was similarly unaffected due to their likeness in chemical structures. In this investigation, the determination of protein binding of anthracyclines was obtained using a concentration of 15 lg/mL.…”

“…The free concentration of anthracyclines was determined using HPLC and their degree of protein binding in serum was reported in the range of 56.9 -63.1% [14]. In another application of equilibrium dialysis, the protein binding of DOX in both human and rat plasma was also determined using HPLC.…”

In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects

“…␣ 1 -Acid glycoprotein (AAG) is the primary plasma-binding protein of both CEP-701 (Cephalon, unpublished data, December 2001) and daunorubicin. [28][29][30] If CEP-701 displaced daunorubicin from its IC50 and CI values for the combination of 10 or 20 nM CEP-701 and chemotherapeutic agents at doses corresponding to the approximate IC50. In this simultaneous treatment scenario, triplicate samples of cells were simultaneously exposed to CEP-701 and the chemotherapeutic agent for 48 hours, and then MTT assays were performed.…”

Human serum albumin: spectroscopic studies of the paclitaxel binding and proximity relationships with cisplatin and adriamycin

“…The reversible binding of anthracyclines and taxanes to serum components was observed, and albumin was suggested to be the major ligand for this family of drugs. About 50-60% of the adriamycin [6] and more than 90% of paclitaxel [7], binds rapidly and extensively to albumin. The principal regions of ligand binding sites of albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry [1].…”