Once-weekly erythropoietic therapy: is there a difference between the available preparations?

Epoetin administration once weekly to renal failure patients is not new, and indeed a series of publications examining this frequency of administration appeared in the early 1990s [1–11]. During the last decade, however, nephrologists largely settled on twiceor thrice-weekly administration for most of their patients, and the small number who end up on once-weekly dosing are generally those who are responding well to epoetin therapy in the maintenance phase of treatment. It is certainly less common to start such patients on once-weekly administration, although a large Austrian multicentre study in pre-dialysis patients did utilize a treatment regimen of 10 000 U of epoetin once weekly [6]. There is little doubt that the introduction of darbepoetin alfa around the middle of last year once again focused our minds on the concept of once-weekly dosing [12]. This product was specifically developed to be a longer-acting erythropoietic agent, with one of its main aims to allow less frequent dosing both intravenously and subcutaneously. This was achieved by adding an extra two N-linked glycosylation chains to the protein backbone of the molecule (which in turn required five amino-acid substitutions) [13], and the extra sialic acid residues that were conferred on the new molecule produced an intravenous half-life of 25.3 h compared with 8.5 h for epoetin-alfa [14]. The pharmacokinetics of a drug, however, do not always predict the pharmacodynamics or biological response, since the latter may be dependent on more than an ambient circulating level of the drug. Thus, some biological effects may require continuous receptor occupancy, while others may be driven by intermittent receptor occupancy. Correspondence and offprint requests to: Dr Iain C. Macdougall, Consultant Nephrologist, Renal Unit, King’s College Hospital, East Dulwich Grove, London SE22 8PT, UK. Email: icm-kru@globalnet.co.uk Nephrol Dial Transplant (2002) 17: 2047–2051