A comparison of My Precise Dose and WAPPS-Hemo as dosing tools for optimizing prophylaxis in children with hemophilia A treated with BAY 81-8973.

BACKGROUND

Dense sampling served as the foundation for the conventional calculation of pharmacokinetic (PK) parameters. Individual PK can now be estimated via sparse sampling thanks to the development of Bayesian population PK (popPK). Both My Precise Dose (MPD) and the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) use the popPK model of BAY 81-8973 to forecast personalized dosage.

OBJECTIVE

To compare the PK profiles and dosage estimates provided by WAPPS-Hemo and MPD for prophylaxis in children with hemophilia A treated with BAY 81-8973.

METHODS

Thirty-eight pediatric patients with severe hemophilia A were enrolled. After a 72-h washout period, each patient received a 50 IU/kg infusion of BAY 81-8973. PK parameters were calculated at three time points: pre-dose, 3 h, and 24 h after infusion. Dosing regimens to maintain FVIII trough levels at 1 and 3 IU/dL were determined using the WAPPS-Hemo and MPD models, respectively.

RESULTS

Among the 38 pediatric patients with a median age of 5.7 years (range: 2.8-11.2 years), the MPD exhibited superior values for the half-life (T1/2) and area under the curve (AUC) in comparison to the WAPPS-Hemo, while demonstrating reduced clearance (CL) and steady-state volume of distribution (VSS). WAPPS-Hemo made more mistakes when predicting FVIII activity at 48 h (28.84 %) and 72 h (50.19 %), but only 12.45 % and 47.44 % of the time when predicting by MPD. Statistical analysis indicated a significant difference between the two techniques regarding individual dosage at both 1 IU/dL and 3 IU/dL. [(1 IU/dL: WAPPS-Hemo 12.1 (9.3, 17.1) vs. MPD 7.3 (5.5, 9.9), P < 0.001; 3 IU/dL: WAPPS-Hemo 36.3 (27.8, 51.3) vs. MPD 21.9 (16.4, 30.0), P < 0.001).].

CONCLUSIONS

The pediatric popPK model such as MPD tailored for conditions can more precisely represent the PK characteristics and metabolic conditions of Chinese children in real-world settings, highlighting its potential utility in the clinical care of hemophilia patients.