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. 2017 Dec:160:76-82.
doi: 10.1016/j.thromres.2017.10.025. Epub 2017 Nov 4.

Pharmacokinetics of dabigatran etexilate and rivaroxaban in patients with short bowel syndrome requiring parenteral nutrition: The PDER PAN study

Y Whitney Cheung  1 , Stefano Barco  2 , Ron A A Mathôt  3 , Erik-Jan van den Dool  4 , An K Stroobants  4 , Mireille J Serlie  5 , Saskia Middeldorp  1 , Michiel Coppens  1
Affiliations

Pharmacokinetics of dabigatran etexilate and rivaroxaban in patients with short bowel syndrome requiring parenteral nutrition: The PDER PAN study

Y Whitney Cheung et al. Thromb Res. 2017 Dec.

Abstract

Background and aims: Patients on parenteral nutrition for short bowel syndrome (SBS) have a high risk of thrombotic complications and are often treated with parenteral anticoagulation. Direct oral anticoagulants are absorbed proximally in the digestive tract and may represent alternative regimens in selected SBS patients. In our pilot study, we provided pharmacokinetics parameters of dabigatran etexilate and rivaroxaban in this setting and compared peak (Cmax), trough (Ctrough) concentrations, and areas-under-the-concentration-time-curve (AUC0-t) to reference values retrieved from phase I-III studies.

Methods: We enrolled 6 adults with a remaining small bowel length≤200cm, normal renal/hepatic function, and intact stomach. In our crossover study, patients were exposed to twice-daily dabigatran etexilate 150mg and once-daily rivaroxaban 20mg.

Results: After 5days of dabigatran dosing, Ctrough and Cmax geometric means were 39μg/L (90% CI: 23-66) and 88μg/L (90% CI: 56-137), respectively; AUC0-12h was 958μg∗h/L (90% CI: 635-1445). After 5days of rivaroxaban dosing, Ctrough and Cmax geometric means were 9μg/L (90% CI: 1-71) and 167μg/L (90% CI: 102-276), respectively; AUC0-24h was 1720μg∗h/L (90% CI: 899-3300). Absorption was negligible in one patient with ultra-short (~15cm) bowel. For dabigatran, Cmax ratio was 0.57 (SD 0.33) and Ctrough ratio was 0.35 (SD 0.44). For rivaroxaban, the mean observed-to-reference ratios AUC0-24h and Cmax ratios were 0.73 (SD 0.32) and 0.76 (SD 0.34), respectively.

Conclusions: While in SBS patients there is some absorption of the oral anticoagulants dabigatran etexilate and rivaroxaban, it appears to be lower than reference values. Plasma drug levels showed significant inter-individual variability.

Keywords: Anticoagulants; Dabigatran etexilate; Parenteral nutrition; Pharmacokinetics; Rivaroxaban; Short bowel syndrome.

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