THE PHARMACOKINETICS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN AFTER SUBCUTANEOUS INJECTION AT DIFFERENT SITES

The pharmacokinetics of recombinant human erythropoietin (RhEPO) were investigated after subcutaneous (s.c.) injection in the thigh and in t he abdominal wall. Eleven healthy subjects, age 24.4 years (median), w ere studied. Each subject received two s. c. injections of 100 U.kg(-1 ) RhEPO dissolved in 1 ml water: one injection in the thigh and anothe r in the abdomen. Serum erythropoietin was measured regularly by radio immunoassay until 144 h after each injection. The mean residence time was significantly longer after injection in the thigh than in the abdo men (32.7 vs 26.2 h). The estimated half-life of absorption was signif icantly longer after injection in the thigh than after abdominal appli cation (14.9 vs 12.3 h). The estimated half-life of elimination was no t significantly different (4.4 vs 4.8 h). The relative difference in t he area under the curve between injection in the abdomen and the thigh in the same subject ranged from -36 % to + 68 % but there was no sign ificant difference in bioavailability. The peak concentration was not significantly different and appeared at around 10 h (C-max thigh, 175 U.l(-1) vs C-max abdomen, 216 U.l(-1)). A twin-peak configuration of t he concentration vs time curve with a significant second peak at 24 h was found after injection in the thigh but not after abdominal injecti on. In conclusion, the mean residence time was longer after administra tion in the thigh, probably due to delayed absorption, but bioavailabi lity was not significantly different. Following injection in the thigh the concentration curve had two peaks. The differences may be due to regional variations in lymph flow and to physical activity. The overal l differences in pharmacokinetics appeared to be too small to recommen d a general preference of the injection site.