BACKGROUND: Extended half-life (EHL) factor VIII (FVIII) products may decrease the burden of prophylactic treatment in haemophilia 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 modelled sampling strategies. RESULTS: Many sampling strategies, including several 2-sample designs, accurately predicted the PK and exposure measures (median absolute error <10%). When samples are only collected during a single visit (i.e., predose + peak), inclusion of prior dose information reduces median half-life error from >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-h trough from 25% to <12% in the youngest population. CONCLUSIONS: The PK of rFVIIIFc can be accurately estimated using only peak and trough samples, provided that knowledge of prior doses is incorporated and the PK study is planned on an appropriate day within the dosing regimen.
BACKGROUND: Extended half-life (EHL) factor VIII (FVIII) products may decrease the burden of prophylactic treatment in haemophilia 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 modelled sampling strategies. RESULTS: Many sampling strategies, including several 2-sample designs, accurately predicted the PK and exposure measures (median absolute error <10%). When samples are only collected during a single visit (i.e., predose + peak), inclusion of prior dose information reduces median half-life error from >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-h trough from 25% to <12% in the youngest population. CONCLUSIONS: The PK of rFVIIIFc can be accurately estimated using only peak and trough samples, provided that knowledge of prior doses is incorporated and the PK study is planned on an appropriate day within the dosing regimen.
Authors: Alanna McEneny-King; Alfonso Iorio; Gary Foster; Andrea N Edginton Journal: Expert Opin Drug Metab Toxicol Date: 2016-08-19 Impact factor: 4.481
Authors: Jerry S Powell; Neil C Josephson; Doris Quon; Margaret V Ragni; Gregory Cheng; Ella Li; Haiyan Jiang; Lian Li; Jennifer A Dumont; Jaya Goyal; Xin Zhang; Jurg Sommer; Justin McCue; Margaret Barbetti; Alvin Luk; Glenn F Pierce Journal: Blood Date: 2012-01-05 Impact factor: 22.113
Authors: G Young; J Mahlangu; R Kulkarni; B Nolan; R Liesner; J Pasi; C Barnes; S Neelakantan; G Gambino; L M Cristiano; G F Pierce; G Allen Journal: J Thromb Haemost Date: 2015-04-23 Impact factor: 5.824
Authors: Johnny Mahlangu; Jerry S Powell; Margaret V Ragni; Pratima Chowdary; Neil C Josephson; Ingrid Pabinger; Hideji Hanabusa; Naresh Gupta; Roshni Kulkarni; Patrick Fogarty; David Perry; Amy Shapiro; K John Pasi; Shashikant Apte; Ivan Nestorov; Haiyan Jiang; Shuanglian Li; Srividya Neelakantan; Lynda M Cristiano; Jaya Goyal; Jurg M Sommer; Jennifer A Dumont; Nigel Dodd; Karen Nugent; Gloria Vigliani; Alvin Luk; Aoife Brennan; Glenn F Pierce Journal: Blood Date: 2013-11-13 Impact factor: 22.113