Dose-dependent effects of recombinant human erythropoietin on the reticulocyte population of rabbits.

The effects of repeated applications of recombinant human erythropoietin (rhEPO, epoetin beta, Recormon, CAS 122312-54-3) on the reticulocyte count and the reticulocyte maturation distribution of rabbits were investigated using the automated reticulocyte analysis system Sysmex R-1000. Therefore, 150, 300, and 600 IU rhEPO per animal were injected 3 times in intervals of 5-6 weeks. The strongest reaction was found on the second day after application of rhEPO with respect to maturation distribution characterized by the distribution quotient (DQ) and on the fourth day with respect to reticulocyte count. At this time these parameters showed a distinct dose dependence (p < 0.001). The effect of rhEPO on the erythropoietic system in the same rabbit population could be repeated. Thus, immunological neutralization of rhEPO did not take place in rabbits in response to a 3-fold application. The results indicate a potential basis for a simple bioassay in order to determine rhEPO activity in normocythemic rabbits.