J. D. Williams

PHARMACOKINETICS OF RECOMBINANT HUMAN ERYTHROPOIETIN IN PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL DIALYSIS

To determine the optimum regimen for giving recombinant human erythropoietin (EPO) to patients on continuous ambulatory peritoneal dialysis (CAPD), the pharmacokinetics of single-dose EPO administered intravenously (120 U/kg), intraperitoneally (50,000 U), and subcutaneously (120 U/kg) was investigated. After intravenous administration serum EPO levels decayed exponentially from a peak of 3959 mU/ml, with a half-life of 8.2 h. 2.3% of the total intravenous dose was lost in the dialysate during the first 24 h. Peak serum EPO levels of 375 mU/ml at 12 h and 176 mU/ml at 18 h were attained following intraperitoneal and subcutaneous administration, respectively. The bioavailability of subcutaneous EPO (21.5%) was seven times greater than that of intraperitoneal EPO (2.9%). These results suggest that subcutaneous EPO represents the most satisfactory route of administration for CAPD patients.

Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm.

Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required.

The use of erythropoietin in renal failure.

The treatment of renal anaemia by recombinant human erythropoietin (EPO) is now well established. Several studies have examined the pharmacokinetics and efficacy of the drug given intravenously, intraperitoneally and subcutaneously and there is increasing evidence that the subcutaneous route has several advantages including the requirement for a lower dose. It is also important to stress the need for careful determination of baseline iron status of all patients before commencing EPO therapy. In the long term the extremely high iron stores of transfusion dependent patients will disappear. In the short term, however, the majority of the patients whose serum ferritin is less than 100 micrograms/l will require iron supplementation to allow an appropriate haemoglobin response. Alternatively, a fall in transferrin saturation to less than 20% is certainly an indication for iron supplementation and if oral iron therapy is not adequate then intravenous preparations may have to be considered. Although the anaemia of renal failure can be fully corrected by EPO, partial correction may be sufficient to reverse the problems of reduced exercise capacity, myocardial ischaemia and cardiomegaly which are frequently associated with end-stage renal disease. Partial correction will also result in a lesser rise in whole blood viscosity and, in turn, possibly reduce hypertension, thrombosis and increased peripheral resistance and thus lessen the side effects of EPO therapy.