An analysis on distribution and inter-relationships of biomarkers under rivaroxaban in Japanese patients with non-valvular atrial fibrillation (CVI ARO 1). Issue 4 (August 2018)

• Record Type: Journal Article
• Authors: Suzuki, Shinya; Yamashita, Takeshi; Kasai, Hidefumi; Otsuka, Takayuki; Sagara, Koichi
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 33:Issue 4(2018)
• Page Start: 188
• Page End: 193
• Publication Date: 2018-08
• Subjects: Rivaroxaban -- Atrial fibrillation -- Anticoagulation -- Prothrombin time -- Serum concentration -- Population pharmacokinetics; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2018.02.002
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: Prothrombin time (PT) has been widely used for measuring anticoagulation intensity under rivaroxaban therapy, but precise information has not been well established yet. Consecutive 96 non-valvular atrial fibrillation (NVAF) under rivaroxaban between Jan/June, 2015 were recruited. Serum concentration (SC) and PT with 5 representative reagents available in Japan (Neoplastin Plus®, Thromborel S®, Thrombocheck PT®, Thrombocheck PT Plus®, and Recombiplastin®) at 2-4 hours after (peak) and before intake of rivaroxaban (trough) were measured at outpatient clinic in the cardiovascular institute (CVI ARO study 1). Nonlinear mixed-effects modelling was used to model the population pharmacokinetics and pharmacodynamics of rivaroxaban. An oral one-compartment model was employed to describe the population pharmacokinetics of rivaroxaban. The pharmacokinetics of rivaroxaban were affected by creatinine clearance, alanine aminotransferase, and use of CYP3A4 or P-gp inhibitors. PTs with 5 reagents were predicted by pharmacodinamic models with SC, hematocrit, serum albumin, and age, with medium predicting ability (highest/lowest R2 = 0.746/0.658 in Recombiplastin/Thromborel S, respectively). This population analysis in NVAF patients under rivaroxaban therapy demonstrated that pharmacokinetics of rivaroxaban was described by an oral one-compartment model with expected covariates, and can be assessed by PT with available reagents in Japan with medium predicting ability. Graphical abstract: