European Journal of Clinical Pharmacology

, Volume 74, Issue 8, pp 1095–1095 | Cite as

Extracorporeal circulation systems in coronary artery bypass surgery can affect pharmacokinetics of drugs: may altered CYP-mediated liver function be a possible reason?

  • Umit Yasar
  • Melih O. Babaoglu
Letter to the Editor

Dear Editor,

An interesting paper titled “How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass (CABG) surgery patients” by Kokki et al. (2018) reports a markedly decreased bioavailability of metoprolol in the early phase after CABG surgery patients [1]. The study mainly focuses on the effects of different modalities of CABG surgeries namely cardiac surgery and conventional extracorporeal circulation (CECC), miniaturized ECC, and off-pump surgery (OPCAB) and demonstrates no significant difference among the mentioned methods. The same research group published a similar finding on decreased metoprolol bioavailability in their earlier study [2].

Here, we would like to emphasize another confounding factor that may be associated with a possible alteration in drug metabolism during the bypass surgery. Metoprolol is mainly metabolized by cytochrome P450 2D6 (CYP2D6) and suggested as a probe drug for this enzyme in phenotyping [3, 4].

We previously have demonstrated that cardiopulmonary bypass procedure during cardiac surgery altered CYP2C9 activity [5] using losartan as a phenotyping probe drug [6]. We showed a markedly reduced activity of CYP2C9 (assessed as urinary losartan/E-3174, an active metabolite of the parent drug) shortly after the CABG procedure as compared to the activity before the surgery. This decreased activity returned to normal levels about 1 week after the surgery [5].

In the paper by Kokki et al., the effects of three different bypass surgery methods on metoprolol bioavailability have been well described while not much was accounted for altered cytochrome P450-mediated metabolism during the surgery [1]. It is of importance to emphasize that not only metoprolol but also other drug substrates of CYP2D6 [7] such as other beta adrenoceptor blockers, antidepressants, antipsychotics, and other drugs may be similarly affected especially in the subjects with poor metabolizer status for CYP2D6. We would like to draw attention to possible inhibitory effects of CABG procedure on CYP-mediated drug metabolism particularly in the liver.


  1. 1.
    Kokki H, Maaroos M, Ellam S, Halonen J, Ojanpera I, Ranta M, Ranta VP, Tolonen A, Lindberg O, Viitala M, Hartikainen J (2018) How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients. Eur J Clin PharmacolGoogle Scholar
  2. 2.
    Valtola A, Kokki H, Gergov M, Ojanpera I, Ranta VP, Hakala T (2007) Does coronary artery bypass surgery affect metoprolol bioavailability. Eur J Clin Pharmacol 63:471–478CrossRefPubMedGoogle Scholar
  3. 3.
    Frank D, Jaehde U, Fuhr U (2007) Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. Eur J Clin Pharmacol 63:321–333CrossRefPubMedGoogle Scholar
  4. 4.
    Goryachkina K, Burbello A, Boldueva S, Babak S, Bergman U, Bertilsson L (2008) CYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction. Eur J Clin Pharmacol 64:1163–1173CrossRefPubMedGoogle Scholar
  5. 5.
    Babaoglu MO, Yasar U, Yorgancioglu C, Ozyuksel A, Akbulut B, Bozkurt A (2007) Effect of the cardiopulmonary bypass procedure during cardiac surgery on CYP2C9 activity in human. FASEB J 21:A1185–A1185Google Scholar
  6. 6.
    Babaoglu MO, Yasar U, Sandberg M, Eliasson E, Dahl ML, Kayaalp SO, Bozkurt A (2004) CYP2C9 genetic variants and losartan oxidation in a Turkish population. Eur J Clin Pharmacol 60:337–342PubMedGoogle Scholar
  7. 7.
    He ZX, Chen XW, Zhou ZW, Zhou SF (2015) Impact of physiological, pathological and environmental factors on the expression and activity of human cytochrome P450 2D6 and implications in precision medicine. Drug Metab Rev 47:470–519CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacologyHacettepe University Faculty of MedicineAnkaraTurkey

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