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The pharmacokinetics of Biolimus A9 after elution from the BioMatrix II stent in patients with coronary artery disease: The Stealth PK Study

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objectives

This prospective, open-label multicenter study was conducted to assess the pharmacokinetics of Biolimus A9 after elution from BioMatrix II coronary stents. Recent clinical trials have demonstrated the efficacy and safety of Biolimus A9 eluted from different stent platforms. To date, the pharmacokinetics of Biolimus A9 in patients following the deployment of BioMatrix II stents has not yet been studied

Methods

BioMatrix II stents were implanted into 27 patients with coronary artery disease. The primary endpoints of the study were the systemic concentrations of Biolimus A9 after 28 days and 6 months as measured using a sensitive validated liquid chromatography–tandem mass spectrometry assay.

Results

The highest measured blood concentration at any time point was 394 pg/mL. At 28 days and 6 months following stent placement, 51.8 and 100% of patients, respectively, had Biolimus A9 concentrations <10 pg/mL. After 9 months, 100% of the patients were free of major cardiac adverse events (MACE). There was no Biolimus A9 toxicity, no cardiac or non-cardiac deaths, no myocardial infarctions, nor target vessel or target lesion revascularizations during the 9 months of follow-up. No case of acute, subacute, or late stent thrombosis was detected.

Conclusions

Compared to other drug-eluting stents, such as Cypher, BioMatrix II results in relatively low systemic exposure, which may be explained by the ablominal coating of the Biomatrix II stent in combination with Biolimus A9's high lipophilicity.

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Abbreviations

ACT:

Activated clotting time

DES:

drug-eluting stent

HPLC:

high-performance liquid chromatography

LC-MS/MS:

liquid chromatography- tandem mass spectrometry

LLOQ:

lower limit of quantitation

MACE:

major adverse cardiac events

TIMI:

thrombolysis in myocardial infarction

TLR:

target lesion revascularization

TVR:

target vessel revascularization

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Acknowledgments

This study was supported by a grant from Biosensors International, the United States National Institutes of Health (NIH) P30 DK048520, Mass Spectrometry Core (U.C.) and grant 145053 from Ministry of Science and Technology, Republic of Serbia (M.O.). We are grateful to all patients who agreed to participate in this study. Special thanks to M. Markovic, M. Lukic, V. Perovic J. Sojiljkovic, S. Popov, V. Erdelji, R. Simonovic, D. Udovica, S. Draskovic, Z. Stanojkovic, C. Gavrancic, and M. Vuckovic, who took the greatest care to ensure that samples were frozen, stored, and shipped under the appropriate conditions and to all technicians and support staff in all participating hospitals.

STEALTH PK Investigators and Clinical Study Centers:

Clinical Center Serbia, Belgrade: M.Ostojic, M. Nedeljkovic, S. Stojkovic, B. Beleslin, D.Orlic, M. Tomasevic, A. Arandjelovic,

Clinical Center Nis: Z. Perisic, S. Apostolovic, M. Pavlovic

Institute for Cardiovascular Disease Dedinje, Belgrade: D. Sagic, B. Milosavljevic, LJ. Mangovski, Z. Antonic, M. Colic, D. Topic, L. Angelkov

Institute for Cardiovascular Disease, Sremska Kamenica: R. Jung, D. Benz, D. Debeljacki, V. Ivanovic, D. Bikicki

Financial Disclosures

Dr. Ronald Betts is an employee and shareholder of Biosensors International. Dr. Uwe Christians holds a research grant from Biosensors International and has served as a consultant.

Author information

Authors and Affiliations

  1. Medical School, University of Belgrade and Clinical Center of Serbia, Division of Cardiology, Dr Subotic street 8, 11000, Belgrade, Serbia

    Miodrag C. Ostojic

  2. Clinical Centre Nis, Nis, Serbia

    Zoran Perisic

  3. Institute for Cardiovascular Disease Dedinje, Belgrade, Serbia

    Dragan Sagic

  4. Institute for Cardiovascular Disease, Sremska Kamenica, Serbia

    Robert Jung

  5. Clinical Research & Development, Department of Anesthesiology, University of Colorado Denver, Denver, CO, USA

    Yan-Ling Zhang & Uwe Christians

  6. Eurofins Medinet, Aurora, CO, USA

    Jamie Bendrick-Peart

  7. Biosensors International–USA, Newport Beach, CA, USA

    Ronald Betts

Authors
  1. Miodrag C. Ostojic
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  3. Dragan Sagic
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  4. Robert Jung
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  8. Uwe Christians
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Correspondence to Miodrag C. Ostojic.

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Ostojic, M.C., Perisic, Z., Sagic, D. et al. The pharmacokinetics of Biolimus A9 after elution from the BioMatrix II stent in patients with coronary artery disease: The Stealth PK Study. Eur J Clin Pharmacol 67, 389–398 (2011). https://doi.org/10.1007/s00228-010-0895-1

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  • DOI: https://doi.org/10.1007/s00228-010-0895-1

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