Figure 2.

Characteristics and information content of an individual PK profile. The individual plasma activity level vs. time profile contains most of the information needed to identify the dose and interval for the optimal regimen for a specific patient. We are using as an example plots produced with WAPPS‐Hemo (http://www.wapps-hemo.ca). Panel A represents a profile from a simulated patient dosed with 2500 IU FVIII and plasma activity levels measured at 4, 24, and 48 h post‐administration (small hollow circles and interpolated line). Using a PopPK model and a Bayesian approach the fitted plasma activity level vs time profile is produced (solid black line) with its associated uncertainty (prediction intervals as derived from the underlying PopPK model—dashed grey lines). Estimates of terminal half‐life and time to threshold levels (95% prediction intervals) are clinically actionable outcomes. Panel B presents the process of simulation using patient specific PK. The original measured plasma activity levels (red) and model fit (green) for the 2500‐IU dose are presented for reference. For the patient in Panel A, Panel B shows the weekly profile (solid blue line) on their current regimen of 2500 IU infused every third day. The trough was estimated at 0.03 IU/mL with a weekly consumption of 5833 IU. Assuming a safety threshold of 0.05 IU/mL for the intended level of activity, the time spent below 0.05 IU/mL is estimated to be 13 hours per interval. Panel C shows the calculated curve obtained by keeping the interval at every third day, and increasing the dose at 4000 IU. This would increase the trough level to 0.047 IU/mL and the weekly consumption to 9333 IU. The time spent below 0.05 IU/mL would be 2 hours. Panel D shows the calculated curve obtained by reducing the frequency to every second day and the dose to 1400 IU. This would increase the trough level to 0.05 IU/mL with no time spent below and the weekly consumption would be 4900 IU