Skip to main content
SpringerLink
Log in

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers.

Methods

The study was conducted in 11 healthy men aged 47–57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug.

Results

The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported.

Conclusion

The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AUC:

Area under the curve

C max :

Maximal plasma concentration

t max :

Time to maximal plasma concentration

t 1/2 :

Elimination half-life

SD:

Standard deviation

IMP:

Investigational medicinal product

PiB:

Powder in a bottle

AE:

Adverse event

SAE:

Serious adverse event

TEAE:

Treatment emerged adverse event

CK:

Creatine phosphokinase

References

  1. Acharya M, Bernard A, Gonzalez M, Jiao J, De Vries R, Tran N (2012) Open-label, phase I, pharmacokinetic studies of abiraterone acetate in healthy men. Cancer Chemother Pharmacol 69(6):1583–1590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Attard G et al (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 26(28):4563–4571

    Article  CAS  PubMed  Google Scholar 

  3. EMA/CHMP/542871 (2011) Assessment report for Zytiga procedure no.: EMEA/H/C/002321. Assessment, vol. 44

  4. Chi KN et al (2015) Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer. J Clin Pharmacol 55(12):1406–1414

    Article  CAS  PubMed  Google Scholar 

  5. Geboers S et al (2016) The effect of food on the intraluminal behavior of abiraterone acetate in man. J Pharm Sci 105(9):2974–2981

    Article  CAS  PubMed  Google Scholar 

  6. Li R et al (2012) Abiraterone inhibits 3b-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer Res 18(13):3571–3579

    Article  CAS  PubMed  Google Scholar 

  7. Matteucci ME, Brettmann BK, Rogers TL, Elder EJ, Williams RO, Johnston KP (2007) Design of potent amorphous drug nanoparticles for rapid generation of highly supersaturated media. Mol Pharm 4(5):782–793

    Article  CAS  PubMed  Google Scholar 

  8. Angi R et al (2014) Novel continuous flow technology for the development of a nanostructured Aprepitant formulation with improved pharmacokinetic properties. Eur J Pharm Biopharm 86(3):361–368

    Article  CAS  PubMed  Google Scholar 

  9. Solymosi T et al (2015) Sirolimus formulation with improved pharmacokinetic properties produced by a continuous flow method. Eur J Pharm Biopharm 94:135–140

    Article  CAS  PubMed  Google Scholar 

  10. Niesz K, Wootsch A, Groualle A, Ötvös Z, Darvas F (2009) Instrument and process for nanoparticles production in continous flow mode. WO 2009/133418 A1

  11. Center for Drug Evaluation and Research (2011) NDA 202-379, Clinical pharmacology and biopharmaceutics review(s). p 20, table 5. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202379Orig1s000ClinPharmR.pdf. Accessed 31 July 2017

Download references

Author information

Authors and Affiliations

  1. NanGenex Inc., 47-49 Madarász Viktor u, Budapest, 1138, Hungary

    Tamás Solymosi, Zsolt Ötvös, Réka Angi, Betti Ordasi, Tamás Jordán, László Molnár, Genovéva Filipcsei & Hristos Glavinas

  2. Quotient Clinical Ltd., Mere Way, Ruddington, Nottingham, NG11 6JS, UK

    John McDermott, Vanessa Zann, Ann Church & Stuart Mair

  3. Druggability Technologies Holdings Ltd., Tower Business Centre, Tower Street, Swatar, BKR 4013, Malta

    Gábor Heltovics

Authors
  1. Tamás Solymosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zsolt Ötvös
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Réka Angi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Betti Ordasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tamás Jordán
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. László Molnár
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John McDermott
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vanessa Zann
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ann Church
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stuart Mair
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Genovéva Filipcsei
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gábor Heltovics
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hristos Glavinas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hristos Glavinas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Solymosi, T., Ötvös, Z., Angi, R. et al. Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect. Cancer Chemother Pharmacol 80, 723–728 (2017). https://doi.org/10.1007/s00280-017-3406-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-017-3406-6

Keywords

Search

Navigation