SUBCUTANEOUS ERYTHROPOIETIN

406 bacteria and parasites, fungi, active autoimmune disease, and malignancies.4 In viral diseases neopterin levels rise before antibodies become measurable and they are also raised in symptomless infections and do not depend greatly upon the specific

TABLE I-HAEMOGLOBIN LEVELS IN PATIENTS ON EPO THERAPY GIVEN INTRAVENOUSLY ONE TO THREE TIMES A WEEK OR

SUBCUTANEOUSLY DAILY

of the virus. In the Austrian Tyrol, since October, 1986, all blood donations have been tested for neopterin (besides hepatitis B surface antigen, syphilis, and antibody to HIV-1) and serum alanine aminotransferase activity (ALT). This additional test would, it was hoped, exclude donors with a wide variety of potentially harmful diseases and prevent a repeat of the tragedy of HIV-1in donated blood, if a new virus were to emerge. The neopterin test has now been done on more than 75 000 donors: the additional loss of donations has been 1-6%, less than the loss associated with ALT testing (2-1%). The reasons for raised neopterin levels in blood donors were sought retrospectively and found to include a variety of conditions which would have led to exclusion from donation, had they been known about at the time. These included acute infections with cytomegalovirus and Toxoplasma gondii, respiratory tract infections, autoimmune diseases, and malignant diseases (including an acute myeloblastic nature

leukaemia). In the Austrian Tyrol neopterin testing of blood donations will be continued: the loss of donors has been low, the test has been successfully implemented in the daily laboratory routine, and the safety of donations has been improved. Central Institute for Blood Transfusion, Department of Immunology, and Institute for Medical Chemistry and Biochemistry, University of Innsbruck; and Ludwig Boltzmann Institute for AIDS Research, A-6020 Innsbruck, Austria

,

,

,

i

,

,

I

_

,

I

,

,

,

,

i *Alternating once/twice weekly in patients I and 2; twice weekly in patient 3; thrice weekly in patient 4.

†Daily. TABLE II-HAEMOGLOBIN LEVELS IN PATIENTS ON INTERMITTENT

INTRAVENOUS EPO OR HALF THE DOSE SUBCUTANEOUSLY THRICE WEEKLY

MARTIN HÖNLINGER GILBERT REIBNEGGER DIETHER SCHÖNITZER HELMUT WACHTER

1.

Reibnegger G, Auhuber I, Fuchs D, et al. Urinary neopterin levels in acute viral hepatitis. Hepatology (in press). 2. Prior C, Fuchs D, Hausen A, et al. Potential of urinary neopterin excretion in differentiating chronic non-A, non-B hepatitis from fatty liver. Lancet 1987; ii: 1235-37. 3. Huber C, Batchelor JR, Fuchs D, et al. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon gamma. J Exp Med 1984; 160: 310-16. 4. Fuchs D, Hausen A, Reibnegger G, et al. Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunol Today 1988; 9: 150-55

SUBCUTANEOUS ERYTHROPOIETIN

SiR,-Recombinant human erythropoietin (rhEPC) has revolutionised the treatment of anaemia in patients on maintenance haemodialysis.1 However, the ideal dosage and mode of adminstration have yet to be identified. In an uncontrolled study’ we found that rhEPO was more effective in raising reticulocyte counts and haematocrit when given three times weekly rather than only once or twice a week. No information is available on how long the EPO/EPO-receptor interaction must last if the greatest effects of the hormone on marrow precursor are to be achieved. Pharmacokinetically subcutaneous rhEPO seems to have advantages over intravenous injection. After intravenous injection, Egrie et al3 found an exponential decrease in plasma EPO and a half-life of less than 10 h, while after subcutaneous administration peak concentrations were achieved after 8-12 h and maintained for another 12-16 h. With a median weekly dose of 150 U/kg given by one to three injections, as in our previous studies the annual cost of treating a 70 kg man would be about 10 000 Swiss francs (3800). It is thus not only of therapeutic but also of economic importance to compare dose requirement for rhEPO given intravenously or subcutaneously. In a pilot study (table I) four stable patients being treated with rhEPO by intermittent intravenous injection were switched to daily subcutaneous injections via an insulin pen (’PEN U200’; Disetronic Co, Burgdorf, Switzerland). All patients received a weekly rhEPO dose of 2800 U and subsequently either 4480 U throughout or, after 6 weeks, 4480 U followed by 6720 U (table i). The weekly dose required to maintain haemoglobin values at a given level was lower

I

I

I

I

I

*Frequency (per week) one/two in patients A, B, and D; one in C; two in E; three in F; and two/three in G Stable Hb values also m weeks -6, -5, and4(not shown) tThnce weekly Stable Hb values also in weeks 2, 4, 6, and 8 (not shown). tFistula thrombectomy.

with daily subcutaneous administration than with intermittent intravenous administration. To see if the dose lowering was primarily dependent on the route of administration or on the frequency (daily vs one to three times a week), we ran a second trial. Seven patients on intermittent intravenous rhEPO for more than a year were given rhEPO subcutaneously thrice a week. The dose was reduced by 50% (table n) without deterioration in haemoglobin. Subcutaneous rhEPO permits the dose to be lowered. We are now comparing the two routes in respect of risk of antibody formation.

JÜRGEN BOMMER I Medical University Clinic, D-6900 Heidelberg, West Germany

Dialysis Unit, Heidelberg Home

E. RITZ TH. WEINREICH GUDRUN BOMMER T. ZIEGLER

CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effects of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986; ii: 1175-77. 2. Bommer J, Kugel M, Schoeppe W, et al. Dose-related effects of recombinant human erythropoietin on erythropoiesis. Contr Nephrol 1988; 66: 85-93. 3. Egrie JC, Eschbach JW, McGuire T, Adamson JW. Pharmacokinetics of recombinant hyman erythropoietin (rHuEpo) administered to hemodialysis (HD) patients. Kidney Int 1988; 33: 262 (abstr). 1. Winearls