| Autor: |
Momčilović S; Faculty of Medicine, University of Niš, Serbia., Milovanović JR; Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia., Janković SM; Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia., Jovanović A; Faculty of Medicine, University of Niš, Serbia.; Innovation center, University of Niš, Serbia., Tasić-Otašević S; Faculty of Medicine, University of Niš, Serbia., Stanojević D; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia., Krstić M; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia., Šalinger-Martinović S; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia.; Department of Cardiology, Faculty of Medicine, University of Nis, Serbia., Radojković DD; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia., Damjanović M; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia., Živković M; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia., Maričić B; Faculty of Medicine, University of Niš, Serbia., Ranković G, Mihajlović A; Clinic for Cardiovascular Diseases, Clinical Center of Nš, Serbia., Nikolić VN; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Serbia. |
| Abstrakt: |
To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed β1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS. |
