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Clinical Pharmacokinetics of Ombitasvir

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Abstract

Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the treatment of chronic HCV infection. Ombitasvir is predominantly metabolized by amide hydrolysis followed by oxidative metabolism and is a substrate of P-glycoprotein. Ombitasvir displays linear pharmacokinetics with minimal accumulation and is eliminated via metabolism and biliary excretion. A negligible amount of unchanged drug is excreted in urine. Exposures are comparable across Chinese, Japanese, and non-Asian subjects. The pharmacokinetic characteristics of ombitasvir are similar in healthy subjects and HCV-infected patients, and are not appreciably altered by hepatic or renal impairment. Results from several drug interaction studies demonstrated that ombitasvir has a low potential for drug interactions.

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References

  1. Krishnan P, Beyer J, Mistry N, Koev G, Reisch T, DeGoey D, et al. In vitro and in vivo antiviral activity and resistance profile of ombitasvir, an inhibitor of hepatitis C virus NS5A. Antimicrob Agents Chemother. 2015;59(2):979–87.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Menon RM, Polepally AR, Khatri A, Awni WM, Dutta S. Clinical pharmacokinetics of paritaprevir. Clin Pharmacokinet. 2017. doi:10.1007/s40262-017-0520-x.

    Google Scholar 

  3. King JR, Zha J, Khatri A, Dutta S, Menon RM. Clinical pharmacokinetics of dasabuvir. Clin Pharmacokinet. 2017. doi:10.1007/s40262-017-0519-3.

    PubMed  Google Scholar 

  4. Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014;370(3):222–32.

    Article  CAS  PubMed  Google Scholar 

  5. Viekirax. Summary of product characteristics. UK: AbbVie Ltd; 2015.

  6. Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) [US package insert]. North Chicago, IL; AbbVie Inc., 2016.

  7. Technivie (ombitasvir, paritaprevir, and ritonavir tablets). North Chicago, IL: AbbVie Inc.; 2016.

  8. Chayama K, Notsumata K, Kurosaki M, Sato K, Rodrigues L Jr, Setze C, et al. Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients. Hepatology. 2015;61(5):1523–32.

    Article  CAS  PubMed  Google Scholar 

  9. Badri PS, King JR, Polepally AR, McGovern BH, Dutta S, Menon RM. Dosing recommendations for concomitant medications during 3D anti-HCV therapy. Clin Pharmacokinet. 2016;55(3):275–95.

    Article  CAS  PubMed  Google Scholar 

  10. Dumas E, Lawal A, Menon RM, et al. Pharmacokinetics, safety and tolerability of the HCV NS5A inhibitor ABT-267 following single and multiple doses in healthy adult volunteers. J Hepatol. 2011;54(Suppl 1):S475–6.

    Article  Google Scholar 

  11. Epstein M, Felizarta F, Marbury T, Badri P, Mullally V, Pilot-Matias T, et al. Study of ABT-267 2-day monotherapy followed by 12-week combination therapy in treatment-naive patients with chronic HCV genotype 1 infection. J Hepatol. 2013;58(Suppl):S484.

    Article  Google Scholar 

  12. Shen J, Serby M, Surber B, Lee AJ, Ma J, Badri P, et al. Metabolism and disposition of pan-genotypic inhibitor of hepatitis C virus NS5A ombitasvir in humans. Drug Metab Dispos. 2016;44(8):1148–57.

    Article  CAS  PubMed  Google Scholar 

  13. Khatri A, Menon RM, Marbury TC, Lawitz EJ, Podsadecki TJ, Mullally VM, et al. Pharmacokinetics and safety of co-administered paritaprevir plus ritonavir, ombitasvir, and dasabuvir in hepatic impairment. J Hepatol. 2015;63(4):805–12.

    Article  CAS  PubMed  Google Scholar 

  14. Khatri A, Dutta S, Marbury T, Preston RA, Rodrigues L Jr, Wang H, et al. Pharmacokinetics and tolerability of anti-hepatitis C virus treatment with ombitasvir, paritaprevir, ritonavir, with or without dasabuvir, in subjects with renal impairment. Clin Pharmacokinet. 2017;56(2):153–63.

    Article  CAS  PubMed  Google Scholar 

  15. Pockros PJ, Reddy KR, Mantry PS, Cohen E, Bennett M, Sulkowski MS, et al. LO1: safety of ombitasvir/paritaprevir/ritonavir plus dasabuvir for treating HCV GT1 infection in patients with severe renal impairment or end-stage renal disease: The RUBY-I study. J Hepatol. 2015;62:S257.

    Article  Google Scholar 

  16. Polepally AR, Badri PS, Eckert D, Mensing S, Menon RM. Effects of mild and moderate renal impairment on ombitasvir, paritaprevir, ritonavir, dasabuvir, and ribavirin pharmacokinetics in patients with chronic HCV infection. Eur J Drug Metab Pharmacokinet. 2016. doi:10.1007/s13318-016-0341-6 (Epub 10 May 2016).

  17. Mensing S, Eckert D, Sharma S, Polepally AR, Khatri A, Podsadecki TJ, et al. Population pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin in hepatitis C virus genotype 1 infection: analysis of six phase III trials. Br J Clin Pharmacol. 2016. doi:10.1111/bcp.13138 (Epub 23 Sep 2016).

  18. Holkira Pak (ombitasvir/pritaprevir/ritonavir and dasabuvir) product monograph. St-Laurent, QC: AbbVie Corporation; 2016.

  19. Menon RM, Badri PS, Wang T, Polepally AR, Zha J, Khatri A, et al. Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir. J Hepatol. 2015;63(1):20–9.

    Article  CAS  PubMed  Google Scholar 

  20. Badri PS, Dutta S, Wang H, Podsadecki TJ, Polepally AR, Khatri A, et al. Drug interactions with the direct-acting antiviral combination of ombitasvir and paritaprevir-ritonavir. Antimicrob Agents Chemother. 2015;60(1):105–14.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Badri P, Dutta S, Coakley E, Cohen D, Ding B, Podsadecki T, et al. Pharmacokinetics and dose recommendations for cyclosporine and tacrolimus when coadministered with ABT-450, ombitasvir, and dasabuvir. Am J Transplant. 2015;15(5):1313–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Badri PS, Parikh A, Coakley EP, Ding B, Awni WM, Dutta S, et al. Pharmacokinetics of tacrolimus and cyclosporine in liver transplant recipients receiving 3 direct-acting antivirals as treatment for hepatitis C infection. Ther Drug Monit. 2016;38(5):640–5.

    Article  CAS  PubMed  Google Scholar 

  23. Bow DAJ, Liu J, Kavetskaia O, Menon R, de Morais SM, Nijsen M. A mechanistic non-clinical assessment of drug-drug interactions (metabolism and transporters) with the hepatitis C virus (HCV) regimen: ABT-450/r, ombitasvir and dasabuvir. AASLD/EASL Special Conference on Hepatitis C. New York, NY. 3–5 October, 2014.

  24. Khatri A, Dutta S, Dunbar M, Podsadecki T, Trinh R, Awni W, et al. Evaluation of drug-drug interactions between direct-acting anti-hepatitis C Virus combination regimens and the HIV-1 antiretroviral agents raltegravir, tenofovir, emtricitabine, efavirenz, and rilpivirine. Antimicrob Agents Chemother. 2016;60(5):2965–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Polepally AR, King JR, Ding B, Shuster DL, Dumas EO, Khatri A, et al. Drug-drug interactions between the anti-hepatitis C virus 3D regimen of ombitasvir, paritaprevir/ritonavir, and dasabuvir and eight commonly used medications in healthy volunteers. Clin Pharmacokinet. 2016;55(8):1003–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Khatri A, Dutta S, Wang H, Podsadecki T, Trinh R, Awni W, et al. Evaluation of drug-drug interactions between hepatitis C antiviral agents ombitasvir, paritaprevir/ritonavir, and dasabuvir and HIV-1 protease inhibitors. Clin Infect Dis. 2016;62(8):972–9.

    Article  PubMed  Google Scholar 

  27. King JR, Dutta S, Cohen D, Podsadecki TJ, Ding B, Awni WM, et al. Drug-drug interactions between sofosbuvir and ombitasvir-paritaprevir-ritonavir with or without dasabuvir. Antimicrob Agents Chemother. 2015;60(2):855–61.

    Article  PubMed  Google Scholar 

  28. Zha J, Badri PS, Ding B, Uchiyama N, Alves K, Rodrigues-Jr L, et al. Drug interactions between hepatoprotective agents ursodeoxycholic acid or glycyrrhizin and ombitasvir/paritaprevir/ritonavir in healthy Japanese subjects. Clin Ther. 2015;37(11):2560–71.

    Article  CAS  PubMed  Google Scholar 

  29. Khatri A, Trinh R, Zhao W, Podsadecki T, Menon R. Drug-drug interaction between the direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir plus dasabuvir and the HIV antiretroviral agents dolutegravir or abacavir plus lamivudine. Antimicrob Agents Chemother. 2016;60(10):6244–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank AbbVie employees Allison M. Kitten and Sonja J. Causemaker for medical writing support.

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Authors and Affiliations

  1. Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA

    Prajakta S. Badri, Diana L. Shuster, Sandeep Dutta & Rajeev M. Menon

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  1. Prajakta S. Badri
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  2. Diana L. Shuster
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  3. Sandeep Dutta
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  4. Rajeev M. Menon
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Corresponding author

Correspondence to Rajeev M. Menon.

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Funding

The studies summarized in this report were supported by AbbVie, who contributed to the study designs, research, and interpretation of data, and the writing, reviewing, and approving of the publication.

Conflict of interest

Prajakta S. Badri, Diana L. Shuster, Sandeep Dutta, and Rajeev M. Menon are current or former AbbVie employees and may own AbbVie stock or stock options.

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Badri, P.S., Shuster, D.L., Dutta, S. et al. Clinical Pharmacokinetics of Ombitasvir. Clin Pharmacokinet 56, 1103–1113 (2017). https://doi.org/10.1007/s40262-017-0518-4

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