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Aust Prescr. 2017 June; 40(3): 88.
Published online 2017 June 1. doi:  10.18773/austprescr.2017.033
PMCID: PMC5478397

Pharmacokinetics of apixaban

Penny Beirne, Clinical program officer

I have recently been updating information on the new oral anticoagulants for NPS MedicineWise. I used your article1 as a starting point to see what references have been published since 2013.

In reviewing the pharmacokinetics of apixaban, I got confused and so did some further research. I found a Letter to the Editor on the topic.2 It essentially explains that the commonly quoted number of 50% for renal clearance is flawed due to a calculation error between the primary and secondary source.

REFERENCES

1. Chin PK, Doogue MP. Long-term prescribing of new oral anticoagulants. Aust Prescr 2016;39:200-4. https://doi.org/10.18773/austprescr.2016.06810.18773/austprescr.2016.068 [PMC free article] [PubMed] [Cross Ref]
2. Frost C, Boyd RA. The contribution of apixaban renal clearance to total clearance. J Thromb Thrombolysis 2015;40:521-2. https://doi.org/10.1007/s11239-015-1220-810.1007/s11239-015-1220-8 [PMC free article] [PubMed] [Cross Ref]
Aust Prescr. 2017 June; 40(3): 88.
Published online 2017 June 1. doi:  10.18773/austprescr.2017.033

Authors' response

Paul KL Chin, Research fellow and Matthew P Doogue, Associate professor

Paul Chin and Matthew Doogue, the authors of the article, comment:

Penny Beirne highlights the inconsistent reporting in the literature of the fraction of unchanged apixaban excreted in urine. This has also recently been noted by others.1a The key article that informed our estimates of apixaban oral bioavailability was a mass balance study.2a It reported that around 25% of an orally administered dose was excreted unchanged in urine. When corrected for an oral bioavailability of 50%, this translates to a fraction of 0.5 excreted unchanged in urine. However, this estimate is made in the absence of data on intravenously administered apixaban.

Since reviewing the literature following this letter, we found another apixaban pharmacokinetic study.3 It reported that the fraction of apixaban excreted unchanged in urine following intravenous administration was 0.34. We thus concur with Penny Beirne and would like to change the apixaban value for ‘excretion unchanged in urine’ in the Table of our article to 34%.

Footnotes

Editorial note: The original article on long-term prescribing of new oral anticoagulants has been corrected based on this letter from the authors.

REFERENCES

1a. Hellfritzsch M, Damkier P, Pottegård A, Grønlykke T, Grove EL. Inconsistencies in reporting of renal elimination among NOACs: the case of apixaban. Pharmacoepidemiol Drug Saf 2016;25:346-8. https://doi.org/10.1002/pds.391610.1002/pds.3916 [PubMed] [Cross Ref]
2a. Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009;37:74-81. https://doi.org/10.1124/dmd.108.02314310.1124/dmd.108.023143 [PubMed] [Cross Ref]
3. Vakkalagadda B, Frost C, Byon W, Boyd RA, Wang J, Zhang D, et al. Effect of rifampin on the pharmacokinetics of apixaban, an oral direct inhibitor of factor Xa. Am J Cardiovasc Drugs 2016;16:119-27. https://doi.org/10.1007/s40256-015-0157-910.1007/s40256-015-0157-9 [PubMed] [Cross Ref]

Articles from Australian Prescriber are provided here courtesy of NPS MedicineWise