The use of serum bepridil concentration as a safe rhythm control strategy in patients with atrial tachyarrhythmias

Abstract

a b s t r a c tThe aim of this study was to evaluate the clinical significance of serum bepridil (Bep) concentration (SBC) for safely managing patients with atrial tachyarrhythmias (AT). Methods and results: SBC was measured in 37 patients with AT, including atrial fribrillation (AF) (31 cases), AF þ atrial flutter (AFL) (4 cases), AFL (1 case), and atrial tachycardia (1 case). The patients were administrated Bep for more than 4 weeks at the same dose. SBC was positively correlated with Bep dose per kilogram of body weight (p ¼0.015), QT interval (p¼ 0.019), and QTc (p ¼0.034). The patients were divided into 2 groups according to their SBC: the high-SBC (HSBC) group of 8 patients with an SBC Z 500 ng/ml and a low-SBC (LSBC) group of 29 patients with an SBC o 500 ng/ml. There was no difference in maintenance of sinus rhythm between the groups. For clinical variables, QT and QTc were significantly longer in the HSBC than in the LSBC group (p¼ 0.004 and p ¼ 0.016, respectively). Patients with QT 40.5 were more prominent in the HSBC group (37.5% vs. 3.4%, p¼ 0.026), and torsade de points (TdP) occurred in only one patient in the HSBC group. However, there were several patients with normal QT/QTc despite having high SBC. Conclusions: In patients treated with Bep, measurement of SBC is useful for preventing proarrhythmias.

Effect of polypharmacy on plasma bepridil concentration in patients with heart failure: a multicenter retrospective study

“…A meta-analysis revealed that QT prolongation is associated with cardiovascular and sudden death [ 22 ], suggesting that patients with HF should be carefully monitored. Several studies reported that plasma bepridil concentration correlates with the daily dose [ 5 , 14 ], and this phenomenon is consistent with the findings of the present study (Fig. 2 ).…”

“…The following patients were excluded from the analysis as follows: (1) patients with no plasma bepridil measurement, (2) patients without echocardiography data, (3) patients undergoing hemodialysis, and (4) missing data. In this study, patients who had been administered bepridil for at least 28 days beyond the steady state were selected for analysis as previously reported [ 14 ]. Blood samples were stored at 4 °C until measurement.…”

Bepridil is potent against SARS-CoV-2 In Vitro

“…35 In another study, bepridil was administrated at a dose of 100 mg/kg for managing atrial arrhythmias, indicating that it has a very low level of cellular toxicity. 36 Moreover, a previous study showed that bepridil can increase the pH of acidic endosomes. 37 Administration of a high dose of bepridil is expected to have dual functions to slow down the virus replication in host cells by both inhibiting M Pro and raising the pH of endosomes.…”

Guidelines for Therapeutic Drug Monitoring of Cardiovascular Drugs Clinical Use of Blood Drug Concentration Monitoring (JCS 2015) ― Digest Version ―

“…28, 29 Bepridil increases the risk of polymorphic ventricular tachycardia (torsades de pointes), and a relationship between increased bepridil concentration and QT prolongation has been documented. 30- 34 The therapeutic range of bepridil is 250 to 800 ng/mL, and the risk of QT prolongation increases at plasma bepridil concentrations of >800 ng/mL. 33 The clearance of bepridil is low in low-body-weight individuals and elderly individuals.…”