Phillips Marc, Smith William, Balan Guhan, Ward Suzanne
Protherics PLC, The Heath Business & Technical Park, Runcorn, Cheshire, UK.
J Clin Pharmacol. 2008 Mar;48(3):279-84. doi: 10.1177/0091270007311571. Epub 2008 Jan 11.
Glucarpidase (formerly known as carboxypeptidase G2 or CPG2) is being evaluated for the adjunctive treatment of patients experiencing, or at risk of, methotrexate toxicity attributable to its delayed elimination. Delayed elimination of methotrexate can occur in patients with methotrexate-induced renal toxicity. In this study, glucarpidase pharmacokinetics were assessed in volunteer subjects with normal (n = 8) and severely impaired (n = 4) renal function. Each subject received a single intravenous dose of glucarpidase 50 U/kg (equivalent to 114.5 microg/kg) infused over 5 minutes. The mean maximum serum concentration (C(max)) for glucarpidase in renally impaired subjects was 2.9 microg/mL, the mean half-life (t(1/2)) was 10.0 hours, and the mean area under the serum concentration-time curve from time zero to infinity (AUC(0-infinity)) was 24.5 microg x h/mL. Similar values were found in subjects with normal renal function (mean C(max) 3.1 microg/mL, mean t(1/2) 9.0 hours, and mean AUC(0-infinity) 23.4 microg x h/mL). The results indicated little effect of renal impairment on the serum pharmacokinetics of glucarpidase.
羧肽酶G2（以前称为羧肽酶G2或CPG2）正在接受评估，用于辅助治疗因甲氨蝶呤消除延迟而出现或有甲氨蝶呤毒性风险的患者。甲氨蝶呤诱导的肾毒性患者可能会出现甲氨蝶呤消除延迟。在本研究中，对肾功能正常（n = 8）和严重受损（n = 4）的志愿者受试者评估了羧肽酶G2的药代动力学。每位受试者接受单次静脉注射50 U/kg（相当于114.5 μg/kg）的羧肽酶G2，在5分钟内输注完毕。肾功能受损受试者中羧肽酶G2的平均最大血清浓度（C(max)）为2.9 μg/mL，平均半衰期（t(1/2)）为10.0小时，血清浓度-时间曲线从零到无穷大的平均面积（AUC(0-无穷大)）为24.5 μg·h/mL。肾功能正常的受试者也得到了类似的值（平均C(max) 3.1 μg/mL，平均t(1/2) 9.0小时，平均AUC(0-无穷大) 23.4 μg·h/mL）。结果表明肾功能损害对羧肽酶G2的血清药代动力学影响很小。
