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Comparative Study
. 2010 Apr;8(4):730-6.
doi: 10.1111/j.1538-7836.2010.03757.x.

Comparative pharmacokinetics of plasma- and albumin-free recombinant factor VIII in children and adults: the influence of blood sampling schedule on observed age-related differences and implications for dose tailoring

S Björkman  1 , V S Blanchette, K Fischer, M Oh, G Spotts, P Schroth, S Fritsch, L Patrone, B M Ewenstein; Advate Clinical Program Group; P W Collins
Collaborators, Affiliations
Free PMC article
Comparative Study

Comparative pharmacokinetics of plasma- and albumin-free recombinant factor VIII in children and adults: the influence of blood sampling schedule on observed age-related differences and implications for dose tailoring

S Björkman et al. J Thromb Haemost. 2010 Apr.
Free PMC article

Abstract

Background: Dose tailoring of coagulation factors requires reliably estimated and reproducible pharmacokinetics (PK) in the individual patient.

Objectives: To investigate the contribution of both biological and methodological factors to the observed variability of factor VIII (FVIII) PK, with the focus on differences between children and adults, and to examine the implications for dosing.

Patients: Data from 52 1-6-year-old and 100 10-65-year-old patients with hemophilia A (FVIII < or = 2 IU dL(-1)) in three clinical studies were included.

Results: In vivo recovery was lower, weight-adjusted clearance was higher and FVIII half-life was on average shorter in children than in adults. However, a reduced blood sampling schedule for children was estimated to account for up to one half of the total observed differences. Intrapatient variance in PK was smaller than interpatient variance in 10-65-year-olds. Age and ratio of actual to ideal weight only showed weak relationships with PK parameters. Variance in PK caused large variance in the calculated dose required to maintain a target FVIII trough level during prophylactic treatment.

Conclusion: Differences in blood sampling schedules should be taken into account when results from different PK studies are compared. However, even with this consideration, PK cannot be predicted from observable patient characteristics but must be determined for the individual. Because the influence of reducing the blood sampling was minor in comparison to the true variance between patients, a reduced blood sampling protocol can be used. Low intrapatient variability supports the use of PK measurements for dose tailoring of FVIII.

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Figures

Fig. 1
Fig. 1
Representative FVIII:C vs. time curves from two adult patients as evaluated by one- or two-phase linear regression. When the full sampling schedule is used, the fitted curve is monophasic for patient A and biphasic for patient B. With data from the reduced sampling schedule, only monophasic curves can be fitted for both patients. Key to symbols: open and filled circles and dashed line = biphasic fit, filled circles and solid lines = monophasic fit.
See this image and copyright information in PMC

References

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