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
2010
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 £ 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
samplingwas 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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
27
References
102
Citations
NaN
KQI