Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA.
Haemophilia. 2021 May;27(3):351-357. doi: 10.1111/hae.14285. Epub 2021 Mar 22.
Obesity alters the pharmacokinetic (PK) properties of drugs making it difficult to determine the appropriate dose when administering weight-based medications. Alternative descriptors of body weight, such as lean body mass (LBM) and ideal body weight (IBW), are sometimes used in these situations.
We performed a single-centre, randomized, controlled, open-label, 3 × 3 crossover trial to determine whether recombinant factor VIII (rFVIII) dosing based on LBM and IBW achieves a targeted FVIII recovery with better precision than based on total body weight (TBW) in overweight and obese, adult males with haemophilia A. Participants were randomized to 1 of 6 possible FVIII concentrate dosing sequence scenarios (TBW, LBM and IBW). Recombinant FVIII was administered on 3 separate weeks following a washout period of at least 72 hours.
A total of 19 participants were randomized and completed the study. FVIII recovery was lower at 30 minutes post-rFVIII infusion in LBM vs TBW and IBW vs TBW-based dosing, mean difference -0.38 (95% CI: -0.56, -0.20) and -0.28 (95% CI: -0.47, -0.10) IU/dL per IU/kg, respectively. In LBM vs TBW and IBW vs TBW-based dosing, there was a non-significant increase in the proportion of participants with a targeted FVIII recovery of 2.00 ± 0.20 IU/dl per IU/kg, OR = 1.93 (95% CI: 0.44, 8.55) and OR = 3.65 (0.80, 16.72), respectively.
Based on our study's findings, overweight and obese patients with haemophilia A may benefit from an individualized PK analysis using LBM and IBW to determine the most accurate, and potentially cost-effective, method of achieving targeted FVIII recovery.
肥胖改变了药物的药代动力学（PK）特性，使得在给予基于体重的药物时难以确定合适的剂量。在这些情况下，有时会使用身体重量的替代描述符，如瘦体重（LBM）和理想体重（IBW）。
我们进行了一项单中心、随机、对照、开放标签、3×3 交叉试验，以确定在超重和肥胖的成年男性血友病 A 患者中，基于 LBM 和 IBW 的重组因子 VIII（rFVIII）给药是否比基于总体重（TBW）更能实现靶向 FVIII 恢复，且具有更好的精度。参与者被随机分配到 6 种可能的 FVIII 浓缩物给药顺序方案（TBW、LBM 和 IBW）中的 1 种。重组 FVIII 在至少 72 小时洗脱期后分 3 周给予。
共有 19 名参与者被随机分配并完成了研究。在 rFVIII 输注后 30 分钟，LBM 与 TBW 相比和 IBW 与 TBW 相比，FVIII 恢复较低，平均差异分别为-0.38（95%CI：-0.56，-0.20）和-0.28（95%CI：-0.47，-0.10）IU/dL/ IU/kg。在 LBM 与 TBW 相比和 IBW 与 TBW 相比的剂量中，有靶向 FVIII 恢复为 2.00±0.20 IU/dl/ IU/kg 的参与者比例分别增加，但无统计学意义，OR 分别为 1.93（95%CI：0.44，8.55）和 3.65（95%CI：0.80，16.72）。
根据我们研究的结果，血友病 A 的超重和肥胖患者可能受益于使用 LBM 和 IBW 进行个体化 PK 分析，以确定最准确且可能具有成本效益的实现靶向 FVIII 恢复的方法。
