Influence of blood group and von Willebrand factor on population pharmacokinetics and dose individualization of recombinant factor VIII in Taiwanese patients with haemophilia A.

Autor: Singkham N; Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand., Punyawudho B; Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand., Yu MS; Division of Hematology, Conde S. Januário Hospital, Macau, China., Cheng SN; Hemophilia and Rare Disease Treatment Center, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan., Chen SH; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Department of Pediatrics, Shuang Ho Hospital, Ministry of Health and Welfare, Taipei Medical University, Taipei, Taiwan., Chang H; Division of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan., Chen CC; Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.; College of Medicine, Chang Gung University, Tao-Yuan, Taiwan., Hsiao CC; Division of Hematology/Oncology, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.; College of Medicine, Chang Gung University, Kaohsiung, Taiwan., Hou JY; Division of Pediatric Hematology-Oncology, MacKay Children's Hospital, Taipei, Taiwan., Fang YP; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; Regeneration Medicine and Cell Therapy Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Wang HW; Medical Affairs Department, Panco Healthcare, Taipei, Taiwan., Lin JH; Medical Affairs Department, Panco Healthcare, Taipei, Taiwan., Yu LH; Medical Affairs Department, Panco Healthcare, Taipei, Taiwan., Chen YC; Division of Hematology and Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Jazyk: angličtina
Zdroj: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2022 Mar; Vol. 28 (2), pp. 230-238. Date of Electronic Publication: 2022 Jan 20.
DOI: 10.1111/hae.14493
Abstrakt: Introduction: The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost-beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment.
Aim: This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment.
Methods: A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed-effects modelling (NONMEM ® ) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens.
Results: A two-compartment model with first-order elimination best described the rFVIII data. Weight-based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15-40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62-62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL.
Conclusion: The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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