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- Title
An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in Healthy Adults.
- Authors
Duchin, Kenneth; Duggal, Anil; Atiee, George; Kidokoro, Motonori; Takatani, Tadanobu; Shipitofsky, Nicole; He, Ling; Zhang, George; Kakkar, Tarundeep; Atiee, George J; Shipitofsky, Nicole Lazarus
- Abstract
<bold>Background: </bold>Edoxaban is an orally active, direct factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation and for the treatment of venous thromboembolism.<bold>Objectives: </bold>This study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60-mg tablet crushed and administered via a nasogastric tube in a water suspension or orally mixed in apple puree.<bold>Methods: </bold>This phase 1, open-label, crossover study randomized 30 healthy adults to receive three edoxaban treatment regimens (oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered via a nasogastric tube or orally in apple puree) in one of six treatment sequences.<bold>Results: </bold>Total edoxaban exposure was similar between the intact and crushed tablet regimens (mean area under the plasma concentration-time curve from time zero to infinity: whole tablet, 2132 ng·h/mL; nasogastric tube, 2021 ng·h/mL; apple puree, 2076 ng·h/mL). Mean maximum plasma concentration, area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, terminal half-life, and apparent total body clearance values were also similar. Time to maximum plasma concentration was significantly shorter for the nasogastric tube suspension and apple puree vs. the whole tablet [Hodges-Lehmann estimate of median difference (90% confidence interval): -0.75 (-1.25, -0.28); p = 0.0003 and -0.62 (-0.99, -0.26); p = 0.0024, respectively]. The maximum plasma concentation, area under the plasma concentration-time curve from time zero to infinity, and area under the plasma concentration-time curve from time zero to the time of the last measurable concentration were similar between treatment regimens; 90% confidence interval of the geometric least-squares means ratios were within the predefined 80-125% bioequivalence criterion. The safety and tolerability of edoxaban did not differ between treatment regimens.<bold>Conclusion: </bold>The results support the use of edoxaban tablets crushed and administered either via a nasogastric tube or orally mixed in apple puree in patients who are unable to swallow solid oral dose formulations.
- Subjects
PHARMACOKINETICS; ANTICOAGULANTS; DRUG administration; NASOENTERAL tubes; HEALTH of adults; APPLES; COMPARATIVE studies; CROSSOVER trials; DOSAGE forms of drugs; RESEARCH methodology; MEDICAL cooperation; ORAL drug administration; PYRIDINE; RESEARCH; STATISTICAL sampling; GASTRIC intubation; SUSPENSIONS (Chemistry); DRUG tablets; THIAZOLES; TIME; EVALUATION research; RANDOMIZED controlled trials
- Publication
Clinical Pharmacokinetics, 2018, Vol 57, Issue 2, p221
- ISSN
0312-5963
- Publication type
journal article
- DOI
10.1007/s40262-017-0554-0