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How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients

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

Abstract

Purpose

Cardiac surgery and conventional extracorporeal circulation (CECC) impair the bioavailability of drugs administered by mouth. It is not known whether miniaturized ECC (MECC) or off-pump surgery (OPCAB) affect the bioavailability in similar manner. We evaluated the metoprolol bioavailability in patients undergoing CABG surgery with CECC, MECC, or having OPCAB.

Methods

Thirty patients, ten in each group, aged 44–79 years, scheduled for CABG surgery were administered 50 mg metoprolol by mouth on the preoperative day at 8–10 a.m. and 8 p.m., 2 h before surgery, and thereafter daily at 8 a.m. and 8 p.m. Blood samples were collected up to 12 h after the morning dose on the preoperative day and on first and third postoperative days. Metoprolol concentration in plasma was analyzed using liquid chromatography-mass spectrometry.

Results

The absorption of metoprolol was markedly reduced on the first postoperative day in all three groups, but recovered to the preoperative level on the third postoperative day. The geometric means (90% confidence interval) of AUC0–12 on the first and third postoperative days versus the preoperative day were 44 (26–74)% and 109 (86–139)% in the CECC-group, 28 (16–50)% and 79 (59–105)% in the MECC-group, and 26 (12–56)% and 96 (77–119)% in the OPCAB-group, respectively. Two patients in the CECC-group and two in the MECC-group developed atrial fibrillation (AF). The bioavailability and the drug concentrations of metoprolol in patients developing AF did not differ from those who remained in sinus rhythm.

Conclusion

The bioavailability of metoprolol by mouth was markedly reduced in the early phase after CABG with no difference between the CECC-, MECC-, and OPCAB-groups.

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Funding

This study was funded by the governmental VTR-grant by the Hospital District of Northern Savo, Kuopio, Finland and Olvi Säätiö, Iisalmi, Finland.

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Author notes

    Authors and Affiliations

    1. School of Medicine, University of Eastern Finland, Kuopio, Finland

      Hannu Kokki, Jari Halonen & Juha Hartikainen

    2. Department of Anaesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, KYS, Finland

      Hannu Kokki & Sten Ellam

    3. Heart Centre, Kuopio University Hospital, Kuopio, Finland

      Martin Maaroos, Jari Halonen, Aleksandra Tolonen & Juha Hartikainen

    4. Department of Forensic Medicine, University of Helsinki, Helsinki, Finland

      Ilkka Ojanperä & Merja Ranta

    5. School of Pharmacy, University of Eastern Finland, Kuopio, Finland

      Veli-Pekka Ranta

    6. StatFinn & EPID Research, Turku, Finland

      Oscar Lindberg & Matias Viitala

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    1. Hannu Kokki
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    Correspondence to Hannu Kokki.

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    Conflict of interest

    The authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    Hannu Kokki and Martin Maaroos contributed equally to this work.

    The Principal Clinical Investigator is Prof. Juha Hartikainen.

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    Kokki, H., Maaroos, M., Ellam, S. et al. How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients. Eur J Clin Pharmacol 74, 785–792 (2018). https://doi.org/10.1007/s00228-018-2437-1

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    • DOI: https://doi.org/10.1007/s00228-018-2437-1

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