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 the abdominal wall. Eleven healthy subjects, age 24.4 years (median), were 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 another in the abdomen. Serum erythropoietin was measured regularly by radioimmunoassay until 144 h after each injection. The mean residence time was significantly longer after injection in the thigh than in the abdomen (32.7 vs 26.2 h). The estimated half-life of absorption was significantly longer after injection in the thigh than after abdominal application (14.9 vs 12.3 h). The estimated half-life of elimination was not significantly different (4.4 vs 4.8 h). The relative difference in the 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 significant difference in bioavailability. The peak concentration was not significantly different and appeared at around 10 h (Cmax thigh, 175 U.l-1 vs Cmax abdomen, 216 U.l-1). A twin-peak configuration of the concentration vs time curve with a significant second peak at 24 h was found after injection in the thigh but not after abdominal injection. In conclusion, the mean residence time was longer after administration in the thigh, probably due to delayed absorption, but bioavailability 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Nephrology and Medicine C, Skejby Hospital, University Hospital in Aarhus, Denmark.
J D
JD
Jensen
L W
LW
Jensen
J K
JK
Madsen
D000005:Abdomen; D000042:Absorption; D000328:Adult; D001682:Biological Availability; D004921:Erythropoietin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013848:Thigh
D011994:Recombinant Proteins; D004921:Erythropoietin