This review (with 106 references) mainly deals with the analytical applications of flavin-adenine dinucleotide (FAD) fluorescence. In the first section, the spectroscopic properties of this compound are reviewed at the light of his different acid-base, oxidation and structural forms; the chemical and spectroscopic properties of flavin mononucleotide (FMN) and other flavins will be also briefly discussed. The second section discusses how the properties of FAD fluorescence changes in flavoenzymes (FvEs), again considering the different chemical and structural forms; the glucose oxidase (GOx) and the choline oxidase (ChOx) cases will be commented. Since almost certainly the most reported analytical application of FAD fluorescence is as an auto-indicator in enzymatic methods catalysed by FvE oxidoreductases, it is important to know how the concentrations of the different forms of FAD changes along the reaction and, consequently, the fluorescence and the analytical signals. An approach to do this will be presented in section 3. The fourth part of the paper compiles the analytical applications which have been reported until now based in these fluorescence properties. Finally, some suggestions about tentative future research are also given.

Background/Aims: Darbepoetin alfa is an erythropoiesis-stimulating protein that works via the same mechanism and has a threefold longer serum half-life than recombinant human erythropoietin (rHuEPO). The objective of this study was to evaluate extending the dosing interval of darbepoetin alfa to once every other week administration for the treatment of anemia in patients with chronic kidney disease (CKD) not requiring dialysis who were naive to rHuEPO therapy. Methods: This was a multi-center, open-label study. Seventy-six rHuEPO-naive patients were enrolled to receive darbepoetin alfa (0.75 µg/kg) once every other week for up to 24 weeks. Doses were titrated to achieve and maintain a hemoglobin target of 11.0 to 13.0 g/dl. Results: Ninety-seven percent (95% CI: 0.92, 1.00) of patients completing 24 weeks of treatment achieved a hemoglobin response. The median time to response was 5 weeks (range 1–25 weeks). The median darbepoetin alfa dose at the time of response was 60 µg (range 30–130 µg). Darbepoetin alfa was safe and well tolerated, and no antibodies to darbepoetin alfa were detected. Conclusion: These results demonstrate the utility of darbepoetin alfa administered once every other week in rHuEPO-naive CKD patients. This new treatment paradigm may allow for more widespread management of anemia in patients with CKD.

Aim: This multicenter, open-label study determined safety and efficacy of once-every-other-week administration of darbepoetin alfa for anemia of chronic kidney disease in erythropoietin-naive patients not on dialysis. Methods: Participants with hemoglobin levels <11.0 g/dl at baseline were administered darbepoetin alfa at an initial dosage of 0.75 µg/kg once every other week. The dose was titrated to achieve and maintain a hemoglobin response, defined as a hemoglobin range of between 11.0 and 13.0 g/dl for up to 24 weeks. The primary end point was the dose of darbepoetin alfa at initial hemoglobin response. Results: Six hundred and eight patients were enrolled, and 463 completed the study; 95% (95% confidence interval: 0.93, 0.97) of the patients who completed treatment achieved a hemoglobin response. The mean darbepoetin alfa dose at the time of response was 63.5 ± (SD) 16.9 µg, and the mean time to hemoglobin response was 5.7 ± (SD) 4.5 weeks. Oral iron therapy was administered to 60% and intravenous iron to 16% of the participants. Darbepoetin alfa was well tolerated, and adverse events were consistent with those expected in patients with chronic kidney disease. Conclusion: Darbepoetin alfa administered once every other week is effective and safe for achieving and maintaining target hemoglobin levels in anemic patients with chronic kidney disease.

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