Kacirova Ivana, Lazarova Marie, Urinovska Romana, Dodulik Jozef, Drienikova Diana, Vaclavik Jan
Department of Clinical Pharmacology, Institute of Laboratory Medicine, University Hospital Ostrava, Ostrava, Czech Republic.
Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
Pharmacol Res Perspect. 2025 Jun;13(3):e70089. doi: 10.1002/prp2.70089.
Bisoprolol is a second-generation, highly selective beta-1 adrenergic receptor antagonist with various beneficial effects in patients with heart failure. Interindividual variability in response to bisoprolol is known, and finding the optimal dose for individual patients with heart failure is still challenging. This pilot study included patients treated with bisoprolol for chronic heart failure with reduced ejection fraction. Between November 2022 and November 2023, one to six blood samples were collected from these patients to determine the trough serum concentration of bisoprolol. At the same time, the values of selected clinical variables were recorded. Bisoprolol concentrations ranged from 1.1 to 65.0 μg/L and correlated with both the daily dose and the dose per kilogram of body weight. However, wide variability in measured serum concentrations of bisoprolol was observed at the same daily dose and in apparent weight-adjusted clearance. Patients classified as NYHA III-IV received a 33% higher dose per kilogram of body weight than patients in NYHA I-II but achieved 165% higher serum concentrations of bisoprolol. An inverse correlation was found between diastolic blood pressure and dose per kilogram of body weight, and a positive correlation between N-terminal pro-B-type natriuretic peptide and both dose per kilogram of body weight and serum bisoprolol concentration. A wide variability in patients' serum concentrations of bisoprolol achieved after taking the same dose has been observed. A significantly higher concentration-to-dose ratio and a significantly lower weight-adjusted apparent clearance were demonstrated in patients with reduced cardiac function, reduced renal function, and taking the combination with amiodarone. These patients may be more prone to overdose with bisoprolol.
比索洛尔是第二代高选择性β-1肾上腺素能受体拮抗剂，对心力衰竭患者具有多种有益作用。已知患者对比索洛尔的反应存在个体差异，为心力衰竭个体患者找到最佳剂量仍然具有挑战性。这项前瞻性研究纳入了接受比索洛尔治疗射血分数降低的慢性心力衰竭患者。在2022年11月至2023年11月期间，从这些患者中采集了1至6份血样，以测定比索洛尔的谷浓度。同时，记录选定临床变量的值。比索洛尔浓度范围为1.1至65.0μg/L，与每日剂量和每千克体重剂量均相关。然而，在相同每日剂量和表观体重校正清除率下，观察到比索洛尔实测血清浓度存在很大差异。纽约心脏协会（NYHA）III-IV级患者每千克体重接受的剂量比NYHA I-II级患者高33%，但比索洛尔血清浓度却高出165%。发现舒张压与每千克体重剂量呈负相关，N末端B型利钠肽前体与每千克体重剂量和血清比索洛尔浓度均呈正相关。服用相同剂量后，观察到患者比索洛尔血清浓度存在很大差异。心功能降低、肾功能降低以及与胺碘酮联合使用的患者表现出显著更高的浓度-剂量比和显著更低的体重校正表观清除率。这些患者可能更容易出现比索洛尔过量。
