O047 - APIXABAN PHARMACOKINETICS IN SHORT BOWEL SYNDROME, PILOT STUDY

O047

APIXABAN PHARMACOKINETICS IN SHORT BOWEL SYNDROME, PILOT STUDY

K. Hronová^1,*, I. Štenglová-Netíková ¹, E. Meisnerová², F. Novák², P. Kozlík³, T. Křížek³, O. Bartošová ¹, O. Slanař¹, D. Michaličková⁴

¹Department of Pharmacology, ²4th Department of Internal Medicine, Charles University, 1st Faculty of Medicine and General University Hospital, ³Department of Analytical Chemistry, Faculty of Science, Charles University, ⁴Department of Pharmacology, Charles University, 1st Faculty of Medicine, Prague, Czech Republic

Rationale: Short bowel syndrome (SBS) is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to the reduced absorptive surface area, the absorption of orally administered drugs can also be impaired. This study aimed to assess how SBS impacts apixaban (API) pharmacokinetics (PK).

Methods: A population PK (PopPK) analysis was carried out using NONMEM version 7.3.0. In total, 69 API steady-state concentrations were obtained from 13 patients (7 male and 6 female), age: 79 (74-82) years, median (interquartile range), 76 (65-80) kg, 62.9 (55.6-80) mL/min) with dosing of 2.5-7.5 mg API twice daily were included in the analysis. The following characteristics of the patients were tested as potential covariates of API PK: sex, age, body weight, body mass index, height, estimated glomerular filtration rate (eGFR), anatomical type of SBS (1-3), extent of dependency on home parenteral nutrition, co-medication with proton pump inhibitors and GLP-2 analogue. AUC and Cmax were calculated based on the final PopPK model.

Results: Observed API plasma concentrations were best described by a one-compartment model with 3 transit absorption compartments, with log-normally distributed interindividual variability (IIV) on clearance (CL), volume of distribution and mean transit time. eGFR was found to be the only significant covariate for CL of API: for every 1 mL/min decrease in eGFR, there was a 0.043 L/h decrease in API CL. AUC_0-∞ and Cmax of an individual were 1021 ng*h/mL and 134 ng/mL, respectively. These values are comparable with the values obtained from the literature for patients with intact GIT with normal renal function (1).

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Conclusion: SBS did not have a significant impact on PopPK model parameters of apixaban in the studied population. Standard dosing of apixaban might be adequate in patients with SBS. Larger studies are required.

References: 1. Frost et al.; Br J Clin Pharmacol, 2013

Disclosure of Interest: None declared