Limited sampling strategies for accurate determination of extended half-life factor VIII pharmacokinetics in severe haemophilia A patients

Autor:	Pierre Chelle, Patricia J. Barker, Alanna McEneny-King, John C. Panetta, Ulrike M. Reiss, Timothy W. Jacobs, Margaret H Goggans, Ellis J. Neufeld
Rok vydání:	2021
Předmět:	Adult Pediatrics medicine.medical_specialty Adolescent Haemophilia A Population 030204 cardiovascular system & hematology Hemophilia A Hemostatics Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Limited sampling medicine Humans education Child Genetics (clinical) education.field_of_study Factor VIII business.industry Half-life Sampling (statistics) Hematology General Medicine medicine.disease 3. Good health Regimen Severe haemophilia A business 030215 immunology Half-Life
Zdroj:	Haemophilia
ISSN:	1365-2516
Popis:	BACKGROUND: Extended half-life (EHL) factor VIII (FVIII) products may decrease the burden of prophylactic treatment in hemophilia A by reducing infusion frequency. However, these products still exhibit wide inter-patient variability and benefit from pharmacokinetic (PK) tailoring. OBJECTIVE: Identify limited sampling strategies for rFVIIIFc, an EHL FVIII product, that produce accurate estimates of PK parameters and relevant troughs. METHODS: We performed a limited sampling analysis on simulated populations of adults, adolescents, and children based on published population PK data. Sampling strategies were evaluated by comparing the error in estimates of half-life, clearance, and trough levels, to a full 6-sample design. Furthermore, we assessed the impact of incorporating knowledge about prior doses, and the day of the PK study within the regimen. We also evaluated the potential inappropriate dose adjustment rate (IDAR) among the modeled sampling strategies. RESULTS: Many sampling strategies, including several 2-sample designs, accurately predicted the PK and exposure measures (median absolute error 20% to ~5% for adults/adolescents. In this same scenario, appropriate scheduling of the PK study decreases likelihood of unmeasurable predose samples, reducing median error on the 72-hour trough from 25% to
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56114893efd98ef36b8a8fe447e27975 https://pubmed.ncbi.nlm.nih.gov/33742733 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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