Pharmacokinetics of Ibutilide in Patients with Heart Failure Due to Left Ventricular Systolic Dysfunction

Tisdale, James E.; Overholser, Brian R.; Sowinski, Kevin M.; Wroblewski, Heather A.; Amankwa, Kwadwo; Borzak, Steven; Kingery, Joanna R.; Coram, Rita; Zipes, Douglas P.; Flockhart, David A.; Kovacs, Richard J.

doi:10.1592/phco.28.12.1461

Cited by 12 publications

(11 citation statements)

References 38 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 59 studies (49 on cardiovascular drugs) investigating 36 drugs (31 cardiovascular) were identified (Tables ). Twelve studies were published in the period 1970–1979 , 20 in the period 1980–1989 , 12 in the period 1990–1999 , 10 in the period 2000–2009 , and five in the period 2010–2018 .…”

Section: Resultsmentioning

confidence: 99%

“…A total of 59 studies (49 on cardiovascular drugs) investigating 36 drugs (31 cardiovascular) were identified (Tables 1-6). Twelve studies were published in the period 1970-1979 [37][38][39][40][41][42][43][44][45][46][47][48], 20 in the period 1980-1989 [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68], 12 in the period 1990-1999 [69][70][71][72][73][74][75][76][77][78][79][80], 10 in the period 2000-2009 [81][82][83][84][85]…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: a critical appraisal of the evidence

Mangoni

Jarmuzewska

2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

Prescribing in heart failure (HF), a common disease state that predominantly affects the older population, is often a challenging task because of the dynamic nature of the condition, requiring frequent monitoring and medication review, the presence of various comorbidities, and the frailty phenotype of many patients. The significant alterations in various organs and tissues occurring in HF, particularly the reduced cardiac output with peripheral hypoperfusion and the structural and functional changes of the gastrointestinal tract, liver and kidney, might affect the pharmacokinetics of several drugs. This review critically appraises the results of published studies investigating the pharmacokinetics of currently marketed cardiovascular and selected non-cardiovascular drugs in HF patients and control groups, identifies gaps in the current knowledge, and suggests avenues for future research in this complex patient population.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: a critical appraisal of the evidence

Mangoni

Jarmuzewska

2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…This clinical effect is supported by previous experimental observations. In anesthetized dogs, ibutilide reduced the current doses associated with 50% successful defibrillation and approximately half of the animals showed spontaneous defibrillation . This salutatory effect was associated with a significant increase in the ventricular effective refractory period (+23.4%) and the duration of monophasic action potentials at 90% repolarization …”

Section: Discussionmentioning

confidence: 99%

“…26 Ibutilide is extensively metabolized in the liver by oxidation to inactive metabolites in a process that is highly dependent on hepatic perfusion, although in patients with stable heart failure the clearance of ibutilide remains unchanged. 27 However, the metabolism of ibutilide in patients with cardiogenic shock has not been studied. In healthy individuals, 80% of ibutilide is excreted in urine but only 7% as unchanged drug.…”

Section: Pharmacokinetics and Pharmacology Of Ibutilidementioning

confidence: 99%

Ibutilide for the control of refractory ventricular tachycardia and ventricular fibrillation in patients with myocardial ischemia and hemodynamic instability

Sendra-Ferrer

González

2019

Cardiovasc electrophysiol

View full text Add to dashboard Cite

Introduction Recurrent ventricular tachycardia (VT) and ventricular fibrillation (VF) in patients with myocardial ischemia requiring hemodynamic support can be refractory to available antiarrhythmic agents and even to cardioversion and defibrillation. The purpose of this study was to report the effect of intravenous ibutilide in patients with a VT and/or VF storm in the presence of incomplete revascularization requiring hemodynamic support. Methods and results Standard continuous telemetry and frequent 12‐lead electrocardiograms were obtained to determine the effect of intravenous Ibutilide in these patients. We studied six consecutive patients (age 60 ± 12 years; five males) with incomplete revascularization and mechanical support (extracorporeal membrane of oxygenation = 2; left ventricular assist device = 4) with VT/VF refractory to lidocaine and amiodarone. Intravenous ibutilide was given as a last resort for management of their ventricular arrhythmias. Intravenous ibutilide (1‐2 mg) allowed restoration of sinus rhythm in three patients with persistent VF that were refractory to multiple defibrillation shocks. When the 24‐hour period before and after ibutilide administration was compared, this drug markedly reduced the number of required cardioversions/defibrillations in all patients from 20 ± 9 to 0.7 ± 0.8 shocks ( P = 0.036). Conclusions In patients with myocardial ischemia requiring hemodynamic support, intravenous Ibutilide demonstrates a potent antiarrhythmic effect and can facilitate defibrillation in patients with refractory VF.

show abstract

“…17 Two standard calibration curves were generated, which ranged from 62.5 to 16,000 pg/mL and 15.63 to 1000 pg/mL for samples containing higher and lower ibutilide concentrations, respectively. Intraday and interday coefficients of variation were ≤7.0%.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Sensitivity to Drug‐Induced QT Interval Lengthening in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction

Tisdale

Overholser

Wroblewski

et al. 2012

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12-lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia-corrected QT (QTF) intervals (EC50) were determined, and areas under the effect (QTF interval vs time) curves (AUECs) were calculated. Ibutilide concentration–QTF relationships were best described by a sigmoidal Emax model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86-1.93] vs 1.82 [1.81-1.84] s·h; P = .04). Median EC50 was lower in the HF group (0.48 [0.46-0.49] vs 1.85 [1.10-3.23] μg/L; P = .008). Sensitivity to drug-induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug-induced TdP.

show abstract

Pharmacokinetics of Ibutilide in Patients with Heart Failure Due to Left Ventricular Systolic Dysfunction

Cited by 12 publications

References 38 publications

The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: a critical appraisal of the evidence

The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: a critical appraisal of the evidence

Ibutilide for the control of refractory ventricular tachycardia and ventricular fibrillation in patients with myocardial ischemia and hemodynamic instability

Enhanced Sensitivity to Drug‐Induced QT Interval Lengthening in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction

Contact Info

Product

Resources

About