Pharmacokinetics of Factor VIII in Adults with Hemophilia: A 24-Hour Single-Sample Study Focused on Trough Levels

成人血友病患者体内因子VIII的药代动力学:一项以谷浓度为重点的24小时单样本研究

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Abstract

In adults with severe hemophilia A, a streamlined approach to pharmacokinetic (PK) studies, which involves fewer Factor VIII determinations and emphasizes the time needed to achieve specific trough levels, presents an appealing option. To determine the PK profile of Factor VIII using a single measurement taken 24 h after a standard prophylactic regimen. Based on these findings, personalized prophylactic recommendations were established. The study included adults with severe hemophilia A undergoing standard prophylaxis without inhibitors. A single determination of Factor VIII was performed 24 h after the usual administration of the concentrate. PK analysis was conducted using the digital tool WAPPS-Hemo. Key parameters analyzed included maximum concentration (Cmax), area under the curve (AUC), half-life (t½), clearance (Cl), volume of distribution (Vd), trough levels, and the need for dose adjustments. A total of 25 patients were enrolled in the study. The median times to reach trough levels of 5, 2, and 1% were 33, 51, and 59 h, respectively. The median values for Cmax, AUC, t½, Cl, and Vd were 0.70 IU/mL, 7170 mg·h/L, 10 h, 0.37 L/h, and 33 L/kg, respectively. The median Factor VIII level at 24 h was 0.07 IU/mL. Dose adjustments were required for 72% of patients to maintain a 5% trough level, 40% for a 2% trough level, and 36% for a 1% trough level. This approach supports personalized prophylaxis in adults with severe hemophilia A by targeting specific trough levels.

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