Factor VIII Pharmacokinetics in Mexican Patients With Hemophilia A

Abstract

Introduction

Treatment of patients with severe hemophilia A requires the replacement of deficient factor VIII. To reach the international standards of care, an optimal dose of factor VIII should be administered based on pharmacokinetic analysis. However, in Mexico factor VIII pharmacokinetics is not used. Therefore, this study aimed to determine, for the first time, the pharmacokinetic parameters of factor VIII in Mexican patients with severe hemophilia A.

Methods

Fifteen samples from patients with severe hemophilia A under prophylactic treatment were analyzed. Factor VIII activity was determined before infusion at 0.25, 0.5, 1.0, 4.0, 8.0, 12, and 48 h after infusion of a standardized dose of factor VIII (40 UI/kg). WinNolin software was used to establish a mono- and bi-compartmental models to obtain the following parameters: area under the curve, maximum activity, in vivo recovery, distribution volume, half-life time, mean residence time, clearance, minimum activity, and elimination constant.

Results

Factor VIII pharmacokinetics was highly variable among our patients who frequently received overdosage of factor VIII. The bi-compartmental model better explained the behavior of factor VIII in patients with hemophilia A.

Conclusions

Compared with the regimens based on body weight, factor VIII pharmacokinetics shows that the response to factor VIII treatment differs greatly among our patients. Our results strongly suggest that factor VIII treatment must be personalized, regardless of body weight. The lack of evidence and experience on factor VIII pharmacokinetics in our country may represent an obstacle to the future use of extended half-life recombinant factor VIII products.