Pharmacokinetics and Disposition

European Journal of Clinical Pharmacology

, Volume 63, Issue 5, pp 471-478

Does coronary artery bypass surgery affect metoprolol bioavailability

  • Antti ValtolaAffiliated withDepartment of Cardiothoracic Surgery, Kuopio University Hospital
  • , Hannu KokkiAffiliated withDepartment of Anesthesiology and Intensive Care, Kuopio University HospitalDepartment of Pharmacology and Toxicology, University of Kuopio Email author 
  • , Merja GergovAffiliated withDepartment of Forensic Medicine, University of Helsinki
  • , Ilkka OjanperäAffiliated withDepartment of Forensic Medicine, University of Helsinki
  • , Veli-Pekka RantaAffiliated withDepartment of Pharmaceutics, University of Kuopio
  • , Tapio HakalaAffiliated withDepartment of Surgery, North Karelia Central Hospital

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Abstract

Background

β-blockers are commonly administered in patients with coronary artery bypass surgery (CABG). Despite this therapy, however, the incidence of postoperative atrial fibrillation (AF) is high (9–19%), and it is unknown why the β-blockers do not reduce the incidence of AF more efficiently. In this pharmacokinetics study, in which the patients acted as their own controls, we have evaluated the bioavailability of perioperative metoprolol tablets in CABG surgery patients.

Methods

Twelve male patients, aged 45–64 years, scheduled for CABG surgery were administered an initial 50 mg metoprolol tartrate tablet orally on the morning of the preoperative day and thereafter at 12-h intervals. Regular blood samples were collected up to 12 h after the first administration of the drug on the preoperative day as well on the first and third postoperative days. The plasma concentration for metoprolol was analyzed (limit of quantification = 0.001 mg/L) using liquid chromatography-tandem mass spectrometry.

Results

The bioavailability of the metoprolol was significantly less on the first postoperative day, with AUC0–12 values ranging from 0.7 to 17.1 (median: 7.2) mg min/L, than on the preoperative day, with AUC0–12 values of 5.1–26.7 (12.6) mg min/L; however, it returned to the preoperative values on the third postoperative day, with AUC0–12 values of 3.5–25.2 (15.2) mg min/L. Similar changes were observed in Cmax values: preoperative Cmax ranged between 0.026 and 0.123 (0.060) mg/L, on the first postoperative day, the Cmax ranged between 0.003 and 0.093 (0.025) mg/L, and on the third postoperative day, the Cmax ranged between 0.009 and 0.136 (0.061) mg/L. There was no correlation between the pharmacokinetic parameters and patient characteristics, but both the preoperative Cmax and C60 correlated significantly with the postoperative Cmax (Pearson correlation coefficient: 0.61–0.72). One patient with one of the lowest rates and extent of metoprolol absorption developed AF.

Conclusion

This study indicates that the bioavailability of metoprolol is markedly reduced when administered in tablet form during the early phase after CABG.

Keywords

Administration Area Under Curve Atrial fibrillation Coronary artery bypass grafting surgery Drug administration routes Metoprolol Oral Pharmacokinetics