Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model
Objective To predict the level at a specified time and design personalised dosing, we proposed a method (Method 1) for estimating coagulation factor VIII (FVIII) pharmacokinetic (PK) parameters using 4 levels within 48 hours after administering a test dose.Design A retrospective study based on virtu...
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| Format: | Article |
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BMJ Publishing Group
2025-07-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/7/e097053.full |
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| author | Xuemei Wu Zipeng Wei Jianxing Zhou Baohua Xu You Zheng Qingxia Liu Shuxia Zhang Maobai Liu, Meijuan Huang Fenge Yang |
| author_facet | Xuemei Wu Zipeng Wei Jianxing Zhou Baohua Xu You Zheng Qingxia Liu Shuxia Zhang Maobai Liu, Meijuan Huang Fenge Yang |
| author_sort | Xuemei Wu |
| collection | DOAJ |
| description | Objective To predict the level at a specified time and design personalised dosing, we proposed a method (Method 1) for estimating coagulation factor VIII (FVIII) pharmacokinetic (PK) parameters using 4 levels within 48 hours after administering a test dose.Design A retrospective study based on virtual populations and real patients.Setting A comprehensive hospital in China.Participants Virtual populations generated by Monte Carlo simulations and retrospectively collected real patient data.Methods PK profiles of FVIII after dosing in the virtual populations were generated from a published population PK model coupled with Monte Carlo simulation. The simulated coagulation factor levels were considered as the reference (Cref). FVIII levels at six sampling points after dosing were estimated with Method 1 and the method proposed by Lisheng Cai (Method 2) and compared with Cref. PK data from three patients with severe haemophilia A were retrospectively collected to further validate the accuracy of the two methods.Results In the adult group, the maximum mean deviations for Methods 1 and 2 were 0.43% (±0.35%) and −36.31% (±6.67%), with corresponding maximum root mean square errors (RMSE) of 0.12% and 28.44%, respectively. For the paediatric group, the maximum mean deviations for Methods 1 and 2 were 0.13% (±0.25%) and −34.27% (±6.74%), with maximum RMSEs of 0.05% and 25.33%, respectively. In three actual patients, mean deviations using Method 1 were 0.32%, 1.34% and 0.24%. Mean deviations using Method 2 were 13.37%, −16.86% and 56.66%.Conclusion The proposed method for estimating FVIII PK parameters and levels demonstrates high accuracy and has the potential for precision dosing. |
| format | Article |
| id | doaj-art-9488ce78da534f77ae267f913b5e4d1b |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-9488ce78da534f77ae267f913b5e4d1b2025-08-20T03:30:10ZengBMJ Publishing GroupBMJ Open2044-60552025-07-0115710.1136/bmjopen-2024-097053Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment modelXuemei Wu0Zipeng Wei1Jianxing Zhou2Baohua Xu3You Zheng4Qingxia Liu5Shuxia Zhang6Maobai Liu,7Meijuan Huang8Fenge Yang91 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China1 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China1 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China1 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China1 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China1 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China3 Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China1 Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China3 Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China3 Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, ChinaObjective To predict the level at a specified time and design personalised dosing, we proposed a method (Method 1) for estimating coagulation factor VIII (FVIII) pharmacokinetic (PK) parameters using 4 levels within 48 hours after administering a test dose.Design A retrospective study based on virtual populations and real patients.Setting A comprehensive hospital in China.Participants Virtual populations generated by Monte Carlo simulations and retrospectively collected real patient data.Methods PK profiles of FVIII after dosing in the virtual populations were generated from a published population PK model coupled with Monte Carlo simulation. The simulated coagulation factor levels were considered as the reference (Cref). FVIII levels at six sampling points after dosing were estimated with Method 1 and the method proposed by Lisheng Cai (Method 2) and compared with Cref. PK data from three patients with severe haemophilia A were retrospectively collected to further validate the accuracy of the two methods.Results In the adult group, the maximum mean deviations for Methods 1 and 2 were 0.43% (±0.35%) and −36.31% (±6.67%), with corresponding maximum root mean square errors (RMSE) of 0.12% and 28.44%, respectively. For the paediatric group, the maximum mean deviations for Methods 1 and 2 were 0.13% (±0.25%) and −34.27% (±6.74%), with maximum RMSEs of 0.05% and 25.33%, respectively. In three actual patients, mean deviations using Method 1 were 0.32%, 1.34% and 0.24%. Mean deviations using Method 2 were 13.37%, −16.86% and 56.66%.Conclusion The proposed method for estimating FVIII PK parameters and levels demonstrates high accuracy and has the potential for precision dosing.https://bmjopen.bmj.com/content/15/7/e097053.full |
| spellingShingle | Xuemei Wu Zipeng Wei Jianxing Zhou Baohua Xu You Zheng Qingxia Liu Shuxia Zhang Maobai Liu, Meijuan Huang Fenge Yang Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model BMJ Open |
| title | Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model |
| title_full | Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model |
| title_fullStr | Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model |
| title_full_unstemmed | Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model |
| title_short | Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model |
| title_sort | development and validation of an innovative approach to estimating fviii levels and designing personalised doses in the prophylactic treatment of haemophilia a based on the principle of the two compartment model |
| url | https://bmjopen.bmj.com/content/15/7/e097053.full |
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