Presurgical pharmacokinetic analysis of a von Willebrand factor/factor VIII (VWF/FVIII) concentrate in patients with von Willebrand’s disease (VWD) has limited value in dosing for surgery
Presurgical pharmacokinetic analysis of a von Willebrand factor/factor VIII (VWF/FVIII) concentrate in patients with von Willebrand’s disease (VWD) has limited value in dosing for surgery
复制标题
冯·维勒布兰德病 (VWD) 患者中冯·维勒布兰德因子/因子 VIII (VWF/FVIII) 浓缩物的术前药代动力学分析对于手术剂量的价值有限
DOI：
10.1111/j.1365-2516.2011.02583.x
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发表时间：
2011
期刊：
影响因子：
3.9
通讯作者：
Garrett E. Bergman
中科院分区：
文献类型：
--
作者：
J. D. Paola;Stefan Lethagen;J. C. Gill;P. Mannucci;Marilyn J. Manco;J. Bernstein;WILLIAM L. Nichols;Garrett E. Bergman
Summary. Optimal doses of von Willebrand Factor/Factor VIII (VWF/FVIII) concentrates for surgical procedures in patients with VWD need to be determined. A prospective, multicenter study was performed that included an initial pharmacokinetic (PK) assessment following a standard dose of VWF/FVIII concentrate (Humate‐P®) to determine individual PK parameters and guide therapeutic dosing during surgery. Forty one subjects received 60 IU kg−1 VWF: RCo. Median plasma levels, half‐life, mean change from baseline and in vivo recovery (IVR) values were determined for VWF:RCo, VWF:Ag, and FVIII: C, and area under the plasma time‐concentration curve (AUC), mean residence time (MRT), clearance, volume of distribution and dose linearity were also assessed for VWF:RCo at various time points. Median baseline VWF:RCo level was 13 IU dL−1 (range, 6–124); with a mean change from baseline >100 IU dL−1 immediately after the infusion, decreasing to 10 IU dL−1 at 48 h postinfusion. The group median incremental in vivo recovery (IVR) for VWF:RCo was 2.4 IU dL−1 per IU kg−1, for VWF:Ag 2.3 IU dL−1 kg−1 and for FVIII:C was 2.7 IU dL−1 per IU kg−1. When analysing individual recovery values on repeated infusions, a very weak correlation was observed between presurgery IVR and IVR for both VWF:RCo and FVIII, measured at various times just prior to and after the surgical procedure. Although group median values were fairly consistent among repeated IVR measurements, the intra‐individual IVR values for FVIII and VWF:RCo with repeated infusions showed a large degree of variability. IVR values obtained from pharmacokinetic analyses performed in advance of anticipated surgery do not reliably predict postinfusion circulating levels of VWF:RCo or FVIII attained preoperatively or with subsequent peri‐operative infusions.
