Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight
Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight
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DOI：
10.1182/blood-2011-07-360594
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发表时间：
2012-01-12
期刊：
影响因子：
20.3
通讯作者：
Collins, Peter W.
中科院分区：
文献类型：
--
作者：
Bjorkman, Sven;Oh, MyungShin;Collins, Peter W.
患者组之间凝血因子的药代动力学（PK）比较可能因研究方案的差异而偏倚，特别是血液采样时间表之间的差异。这可能会影响临床剂量调整，特别是在儿童中。本研究的目的是通过群体PK模型描述因子VIII（FVIII）的PK与年龄和体重的关系。还探讨了减少血液采样的可能性。根据152例重度血友病A患者（1-65岁）的236次重组FVIII输注建立了FVIII PK模型。通过二室模型充分描述了整个年龄范围内FVIII的PK，并且实际上消除了先前报告的问题，该问题是由于血样采集差异导致的，用于比较儿童和成人的结果。FVIII清除率下降和半衰期随年龄增加可被描述为连续功能。将血液采样从11份回顾性减少至5份，对PK参数估计值无重要差异。所获得的结果可用作临床实践中基于PK的FVIII剂量定制的基础，适用于所有年龄组，且采血量最少。（血。2012; 119（2）：612-618）
Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling. (Blood. 2012; 119(2): 612-618)