PMU-Autor/inn/en
Grundbichler MichaelAbstract
In haemophilia A patients factor VIII (FVIII) recovery and half-life can vary substantially. There are parameters known to modulate FVIII pharmacokinetics (PK), but they explain only about 34% of the variability. The aim of this study was to identify new parameters that influence FVIII PK and thus to expand the current knowledge. FVIII PK were determined in 42 haemophilia A patients (37 severe, 5 moderate) without inhibitor. Patients" characteristics and laboratory parameters were evaluated for an association with FVIII PK. We analysed plasma levels of low-density lipoprotein receptor-related protein 1 (LRP1) and protein C (PC) activity, which had been hypothesized to influence FVIII activity. Furthermore, four variations in intron 6 of the LRP1 gene, which had been shown to influence LRP1, were investigated. FVIII half-life differed widely from 6.2 to 20.7 h, with a median of 10.0 h. Patients with blood group O had shorter FVIII half-life compared to patients with non-O blood group (median FVIII half-life 9.0 h vs. 10.4 h, P = 0.018). Age was significantly associated with FVIII half-life (r = 0.32, P = 0.035). Besides age, also VWF antigen (r = 0.52, P < 0.001) and blood group (r = -0.37, P = 0.015) was associated with FVIII half-life. No correlation was found with FVIII- or LRP1-genotype, LRP1 or PC concentrations. Our data showed large differences in FVIII PK between individual patients and revealed age, blood group and VWF levels as important determining factors for FVIII half-life. FVIII genotype or levels of LRP1 or PC had no influence on FVIII PK.
Useful keywords (using NLM MeSH Indexing)
3-O-Methylglucose/pharmacology
Animals
Anions/metabolism*
Cell Line, Tumor
Cell Membrane/metabolism*
Cytosol/metabolism*
Fluorescence Resonance Energy Transfer/methods
Glucose/pharmacology*
Hypertonic Solutions/pharmacology
Hypoglycemic Agents/pharmacology
Hypotonic Solutions/pharmacology
Insulinoma/metabolism
Insulinoma/pathology
Insulinoma/physiopathology
Ion Channels/metabolism*
Membrane Potentials/drug effects
Patch-Clamp Techniques/methods
Protein Transport/drug effects
Rats
Tolbutamide/pharmacology
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