2019
DOI: 10.1002/psp4.12444
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Enhancing the Quality of Rivaroxaban Exposure Estimates Using Prothrombin Time in the Absence of Pharmacokinetic Sampling

Abstract: Prothrombin time (PT) is a measure of coagulation status and was assessed in the majority of patients in the rivaroxaban phase II and III clinical trials as a pharmacodynamic marker. In the absence of sufficient phase III pharmacokinetic (PK) data to provide individual exposure measures for input into rivaroxaban exposure–response analyses, the aim of the present study was to investigate the use of PT‐adjustment approaches (i.e., the use of observed individual PT measurements) to enhance the prediction of indi… Show more

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Cited by 9 publications
(10 citation statements)
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“…47 However, we believe a rivaroxaban-adjusted dosing scheme can be built using strategies such as exposure-matching to the average Rocket AF study patient exposures, as we have used in this report, or response-matching to prothrombin time, as suggested by other researchers. 48 The proposed precision dosing scheme will be evaluated to determine the impact on efficacy/safety outcome by using a hybrid electronic health record-insurance claims database. Several investigators have replicated the ROCKET-AF rivaroxaban clinical trial findings using insurance claims.…”
Section: Rivaroxaban Precision Dosing Strategiesmentioning
confidence: 99%
“…47 However, we believe a rivaroxaban-adjusted dosing scheme can be built using strategies such as exposure-matching to the average Rocket AF study patient exposures, as we have used in this report, or response-matching to prothrombin time, as suggested by other researchers. 48 The proposed precision dosing scheme will be evaluated to determine the impact on efficacy/safety outcome by using a hybrid electronic health record-insurance claims database. Several investigators have replicated the ROCKET-AF rivaroxaban clinical trial findings using insurance claims.…”
Section: Rivaroxaban Precision Dosing Strategiesmentioning
confidence: 99%
“…Trough plasma concentration (C trough ), maximum plasma concentration (C max ) and area under the plasma concentration-time curve from 0 to 24 h (AUC 0-24 ) at steady state were predicted for each patient based on individual characteristics (age, weight, renal function measured as calculated creatinine clearance [CrCl] using the Cockcroft-Gault equation, and sex) and rivaroxaban dose. Using patient characteristics alone to predict individual rivaroxaban exposure might not adequately reflect the expected variability; therefore, a new approach, to enhance model-predicted rivaroxaban exposures based on the collateral correlation between rivaroxaban plasma concentration and measured prothrombin time, was applied as described previously [22]. Exposure-response analyses were performed for all patients who received at least one dose of rivaroxaban.…”
Section: Model-predicted Rivaroxaban Exposurementioning
confidence: 99%
“…Such treatment individualization requires a robust understanding and quantification of the association between exposure and safety and efficacy. Owing to a lack of observed pharmacokinetic data in the phase 3 RECORD trials, individual rivaroxaban exposure was predicted using a previously developed popPK model, individual covariates and PT measurements [23,24]. Using data from the RECORD1-4 studies and individually predicted derived rivaroxaban exposure parameters, post hoc model-predicted exposure-response analyses were performed to assess the impact of rivaroxaban exposure and patient characteristics on clinical outcomes in patients receiving rivaroxaban for VTE-P after elective THR surgery (35 days of treatment) or TKR surgery (12 days of treatment).…”
Section: Introductionmentioning
confidence: 99%