Souillard A, Audran M, Bressolle F, Jaussaud P, Gareau R
Département de Biophysique, Faculté de Pharmacie, Université de Montpellier I, France.
Biopharm Drug Dispos. 1996 Dec;17(9):805-15. doi: 10.1002/(SICI)1099-081X(199612)17:9<805::AID-BDD995>3.0.CO;2-H.
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.
对马皮下注射重组人促红细胞生成素(rHuEpo)后,对其药代动力学进行了研究。四匹马接受了30IU/kg的单次rHuEpo剂量。一匹马每隔48小时接受三次120IU/kg的重复剂量。通过放射免疫测定法测量血浆促红细胞生成素(Epo)。在这两种情况下,均使用一室开放模型以及一级输入和输出速率来评估药代动力学参数。单次给药后消除半衰期、CL/F和Vd/F的平均值(±标准差)分别为12.9±3.34小时、11.8±4.96L/h和233±126L。重复给药后,消除半衰期、CL/F和Vdss/F分别为11.3小时、8.94L/h和145.6L。与基线值相比,单次给予30IU/kg后血液学参数未观察到显著差异。多次高剂量的rHuEpo改变了红细胞、血红蛋白和血细胞比容。根据我们的结果,在反兴奋剂控制程序中,血浆Epo检测仅在最后一次rHuEpo给药后72小时内有助于支持阳性结果。