Comparison of coagulant activity of factor VII and activated factor VII activity assays when used for determination of recombinant activated factor VII levels in plasma
| Autor: | Birgitte Scharling, Thor Aa Skovsted, Gert G Nielsen, Lone Frost Larsen, Judi Møss, Stine Segel, Thomas Klitgaard |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Adolescent Serial dilution Factor VII Deficiency Factor VIIa Pharmacology Hemophilia A Thromboplastin Plasma chemistry.chemical_compound Pharmacokinetics Reference Values Humans Child Blood Coagulation Volume of distribution Chromatography Factor VII biology Coagulants Chemistry Area under the curve Biological activity Hematology General Medicine Middle Aged Recombinant Proteins Recombinant factor VIIa Child Preschool biology.protein Specific activity Blood Coagulation Tests |
| Zdroj: | Blood Coagulation & Fibrinolysis. 18:677-684 |
| ISSN: | 0957-5235 |
| DOI: | 10.1097/mbc.0b013e3282e7febb |
| Popis: | Two assays [coagulant activity of factor VII (FVII:C) and activated factor VII (FVIIa) activity] are currently available for the assessment of factor VII and FVIIa pharmacokinetics. This article presents the results of a comparison of the two assays when applied both in vitro as well as during clinical pharmacokinetic trials of recombinant FVIIa (rFVIIa) administered to healthy individuals and haemophilia patients. The in-vitro data showed that, for the FVII:C assay, plasma samples do not dilute in parallel. For the FVIIa activity assay, dilutions of samples are both parallel and linear with different dilutions of the calibrator. Moreover, intra-assay variation was found to be smaller for the FVIIa activity assay than for the FVII:C assay. When adding different amounts of rFVIIa (0-6 microg/ml) to normal plasma, a mean specific activity of rFVIIa of 48.6 U/mug was observed on applying the FVII:C assay; however, the specific activity decreased with increasing levels of rFVIIa. For the FVIIa activity assay, the mean specific activity was 45.4 IU/mug. Direct comparison of the two activity assays showed that no simple conversion between FVII:C and FVIIa activity measurements are possible. When applying the two assays for pharmacokinetic assessments in two clinical trials, statistically significant different estimates for the area under the curve, half-life, clearance and volume of distribution were obtained. In conclusion, for evaluation of rFVIIa pharmacokinetic properties, activity should be measured with the FVIIa activity assay - which is a more specific and reliable assay of the two available factor VII activity assays, especially when assessing low activity levels. |
| Databáze: | OpenAIRE |
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