Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects

Abstract

Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures.

Population Pharmacokinetics of Apixaban in Subjects With Nonvalvular Atrial Fibrillation

“…4, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 This analysis utilized a two‐stage approach so the majority of PK model development could be performed with data from the phase I and phase II studies (stage 1). Once data from the phase III study became available, the stage 1 models were re‐estimated (updated stage 1) and then redefined with additional covariate testing (stage 2).…”

A Systems Pharmacology Model for Predicting Effects of Factor Xa Inhibitors in Healthy Subjects: Assessment of Pharmacokinetics and Binding Kinetics

“…However, unlike the relatively standardized PT testing, there is no standardization of reagents used for aPTT testing. The variation in coagulometers, the lot‐to‐lot variation of a given manufacturer's reagents, and the different buffers used in aPTT tests may significantly contribute to the varying results 25, 40, 46. It may be that for these reasons, the prediction for apixaban in the aPTT test was not good.…”

“…Study medication was administered orally for seven days. Blood samples were taken to measure PT and aPTT 25. For more details, the reader is referred to the original reports.…”

Determination of Apixaban Levels in Human Plasma by a High-Throughput Liquid Chromatographic Tandem Mass Spectrometry Assay / Determinarea rapidă a apixabanului în plasma umană prin cromatografie de lichide de înaltă performanță cuplată cu spectrometrie de masă în tandem

“…Frost et al studied pharmacokinetics of apixaban after single dose in healthy subjects by a LC-MS/MS method with LLOQ of 1 ng/mL and quantification range of 1 -1000 ng/mL [7]. In another study, Frost et al applied a LC-MS/MS method after solid phase extraction to determine pharmacokinetics of multiple oral doses of apixaban in healthy subjects, LLOQ being also of 1 ng/mL [22]. Cui et al determined pharmacokinetics profile of apixaban after single-and multiple-dose in healthy Chinese subjects using a validated LC-MS/MS method with atmospheric pressure ionization and protein precipitation of samples before the chromatographic analysis (LLOQ of 1 ng/mL) [23].…”

“…There are several pharmacokinetics studies of apixaban [7,[18][19][20][21][22][23] and assessments of different laboratory tests [17,24] that used LC-MS/MS for quantification of apixaban in human plasma.…”