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

• Published in: European journal of clinical pharmacology Vol. 74; no. 6; pp. 785 - 792
• Main Authors: Kokki, Hannu, Maaroos, Martin, Ellam, Sten, Halonen, Jari, Ojanperä, Ilkka, Ranta, Merja, Ranta, Veli-Pekka, Tolonen, Aleksandra, Lindberg, Oscar, Viitala, Matias, Hartikainen, Juha
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018; Springer Nature B.V
• Subjects: Bioavailability; Biomedical and Life Sciences; Biomedicine; Cardiac arrhythmia; Circulatory system; Coronary artery; Fibrillation; Heart diseases; Heart surgery; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metoprolol; Mouth; Pharmacokinetics and Disposition; Pharmacology/Toxicology; Surgery; Postoperative; Metoprolol; Coronary artery bypass grafting surgery; Pharmacokinetics; Area under the curve; Atrial fibrillation
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-018-2437-1

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 AUC 0–12 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.