Pharmacokinetics of anticoagulants apixaban, dabigatran, edoxaban and rivaroxaban in elderly Japanese patients with atrial fibrillation treated in one general hospital

• Published in: Xenobiotica 2019-09, Vol.49 (9), p.1001-1006
• Main Authors: Yamazaki-Nishioka, Miho, Kogiku, Minoru, Noda, Masayuki, Endo, Sumio, Takekawa, Mitsuru, Kishi, Hirohisa, Ota, Miki, Notsu, Yuki, Shimizu, Makiko, Yamazaki, Hiroshi
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - blood; Anticoagulants - pharmacokinetics; Atrial Fibrillation - drug therapy; Dabigatran - administration & dosage; Dabigatran - adverse effects; Dabigatran - blood; Dabigatran - pharmacokinetics; Dose-Response Relationship, Drug; Female; Humans; insufficient dose; Kidney Diseases - chemically induced; Kidney Function Tests; Male; Middle Aged; overdose; pharmacokinetic modeling; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - blood; Pyrazoles - pharmacokinetics; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - blood; Pyridines - pharmacokinetics; Pyridones - administration & dosage; Pyridones - adverse effects; Pyridones - blood; Pyridones - pharmacokinetics; renal impairment; Rivaroxaban - administration & dosage; Rivaroxaban - adverse effects; Rivaroxaban - blood; Rivaroxaban - pharmacokinetics; Thiazoles - administration & dosage; Thiazoles - adverse effects; Thiazoles - blood; Thiazoles - pharmacokinetics
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2018.1524188

Steady-state plasma concentrations of anticoagulants and the time since the previous administration in mainly outpatients with atrial fibrillation administered standard or reduced doses were analyzed for 110 elderly Japanese subjects (mean age, 76 years) treated with apixaban (2.5 or 5.0 mg twice daily), dabigatran etexilate (110 or 150 mg twice daily), edoxaban (30 or 60 mg once daily) or rivaroxaban (10 or 15 mg once daily) at one general hospital. The pharmacokinetics in patients treated with standard and reduced doses of the four anticoagulants using liquid chromatography-tandem mass spectrometry was compared with the concentration ranges estimated using physiologically based pharmacokinetic modeling. Reduced doses of anticoagulants resulted in relatively small pharmacokinetic variations compared with the standard dose. Statistical analyses revealed that renal impairment is likely not the sole determinant factor for high plasma concentrations of apixaban, dabigatran, edoxaban and rivaroxaban. Patients with atrial fibrillation should be treated with the correct doses of oral anticoagulants as specified in the package inserts (e.g. reduced doses for elderly patients, patients with low body weights and in combination with P-glycoprotein inhibitor drugs) to avoid excessive or insufficient doses of direct oral anticoagulants.