Pharmacokinetics and haematological parameters of recombinant human erythropoietin after subcutaneous administrations in horses.
The pharmacokinetics of recombinant human Epo (rHuEpo) were investigated after subcutaneous administration to horses. Four horses received a single 30IU kg-1 dose of rHuEpo. One horse received three repeated doses of 120 IU kg-1 at 48 h intervals. Plasma erythropoietin (Epo) was measured by radioimmunoassay. In both cases pharmacokinetic parameters were evaluated using a one-compartment open model and first-order input and output rates. The mean values (+/-SD) for elimination half-life, CL/F, and Vd/F after a single dose were 12.9 +/- 3.34 h, 11.8 +/- 4.96 L h-1, and 233 +/- 126 L, respectively. After repeated doses, elimination half-life, CL/F, and Vdss/F were 11.3 h, 8.94 L h-1, and 145.6 L, respectively. No significant differences were observed between the haematological parameters after a single 30 IU kg-1 administration compared to baseline values. Multiple and high doses of rHuEpo modified red blood cells, haemoglobin, and hematocrit. According to our results, plasma Epo assay can help, during an antidoping control procedure, to support a positive result only up to 72 h after the last rHuEpo.
Souillard
A
A
Département de Biophysique, Faculté de Pharmacie, Université de Montpellier I, France.
Audran
M
M
Bressolle
F
F
Jaussaud
P
P
Gareau
R
R
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004906:Erythrocyte Count / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006400:Hematocrit; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006736:Horses; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin