Macdougall Iain C, Padhi Desmond, Jang Graham
Department of Renal Medicine, King's College Hospital, London, UK.
Nephrol Dial Transplant. 2007 Jun;22 Suppl 4:iv2-iv9. doi: 10.1093/ndt/gfm160.
The distinct molecular structure of darbepoetin alfa, in both its amino acid sequence and its carbohydrate content, results in a biologic profile with lower binding affinity, longer circulating half-life, and higher in vivo potency compared with the epoetins. The mechanisms responsible for these differences in biological effects have not been fully explained. Pharmacokinetic investigations of darbepoetin alfa using prolonged blood sampling times established that the mean terminal half-life after subcutaneous (SC) administration is 70 to 105 hours. Pharmacodynamic studies were conducted to assess the suitability of darbepoetin alfa for use in weekly or less frequent (once every other week or once a month) dosing regimens to maintain haemoglobin levels in patients with anaemia of renal disease. Regardless of dialysis status, route of administration, or prior treatment with an erythropoiesis-stimulating agent, darbepoetin alfa administered at extended intervals was able to raise or maintain hemoglobin levels to target. More rigorous studies will be needed to confirm these findings.
与促红细胞生成素相比，阿法达贝泊汀独特的分子结构，包括其氨基酸序列和碳水化合物含量，使其具有较低的结合亲和力、更长的循环半衰期和更高的体内效价的生物学特性。造成这些生物学效应差异的机制尚未完全阐明。通过延长采血时间对阿法达贝泊汀进行的药代动力学研究表明，皮下给药后的平均终末半衰期为70至105小时。进行了药效学研究，以评估阿法达贝泊汀用于每周或更低频率（每隔一周或每月一次）给药方案以维持肾病贫血患者血红蛋白水平的适用性。无论透析状态、给药途径或既往是否接受过促红细胞生成刺激剂治疗，延长给药间隔的阿法达贝泊汀均能将血红蛋白水平提高或维持在目标水平。需要更严格的研究来证实这些发现。
