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Clinical pharmacy and clinical trials (including case series)
Evaluation of the antifactor XA chromogenic assay for measuring rivaroxaban plasma concentrations using calibrators and controls
  1. M. Samama,
  2. G. Contant,
  3. T.E. Spiro,
  4. E. Perzborn,
  5. C. Guinet,
  6. Y. Gourmelin,
  7. L. Le Flem,
  8. G. Rohde,
  9. J.L. Martinoli
  1. 1Biomnis Laboratories, R&D, Ivry sur Seine, France
  2. 2Diagnostica Stago SA, R&D, Gennevilliers, France
  3. 3Bayer HealthCare Pharmaceuticals Inc, Global Clinical Development, Montville NJ, USA
  4. 4Bayer HealthCare AG, Global Drug Discovery, Wuppertal, Germany

Abstract

Background Rivaroxaban is an oral, direct Factor Xa inhibitor approved for clinical use for the prevention and treatment of thromboembolic disorders across several indications. Routine coagulation monitoring is not required, but a quantitative determination of rivaroxaban concentrations might be useful in some clinical circumstances.

Purpose This multicentre study evaluated the suitability of a modified antifactor Xa chromogenic assay for the measurement of plasma rivaroxaban concentrations (ng/ml) using rivaroxaban calibrators and controls, and to assess the inter-laboratory precision of the measurement.

Materials and methods Twenty-four centres in Europe and North America were provided with sets of rivaroxaban calibrators (0, 41, 209 and 422 ng/ml) and rivaroxaban pooled human plasma controls (20, 199 and 662 ng/ml; the concentrations were unknown to the participating laboratories). The evaluation was carried out over 10 days by each laboratory using local antifactor Xa reagents as well as a centrally provided, modified STA Rotachrom assay (Diagnostica Stago, Asnières-sur-Seine, France). A calibration curve was produced each day, and day-to-day precision was evaluated by testing three human plasma controls.

Results When using the local antifactor Xa reagents, the measured rivaroxaban concentrations (mean±SD/actual value) were 17±6.4/20, 205±28.2/199 and 668±94.4 (in diluted samples)/662 ng/ml, and the coefficients of variance (CV) were 37.0%, 13.7% and 14.1%, respectively. When the modified STA Rotachrom method was used, the measured±SD/actual values were 18±3.4/20, 199±21.7/199 and 656±65.8 (in diluted samples)/662 ng/ml and the CV were 19.1%, 10.9% and 10.0%, respectively. Satisfactory inter-laboratory precision was achieved using rivaroxaban calibrators regardless of the type of antifactor Xa reagent and instrument used, except for the lowest concentration tested (20 ng/ml) when using the different local reagent/instrument combinations.

Conclusions The results indicate that the antifactor Xa chromogenic method is suitable for measuring a wide range of plasma rivaroxaban concentrations (20–660 ng/ml), covering the expected concentrations after therapeutic doses, by using rivaroxaban calibrators and controls.

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