Aim: To assess the translation of pharmacokinetic-pharmacodynamic (PK-PD) relationships for heart rate effects of PF-00821385 in dog and man.
Methods: Cardiovascular telemetric parameters and concentration data were available for animals receiving active doses (0.5-120 mg kg(-1), n= 4) or vehicle. PF-00821385 was administered to 24 volunteers and pharmacokinetic and vital signs data were collected. PK-PD models were fitted using nonlinear mixed effects.
Results: Compartmental models with linear absorption and clearance were used to describe pharmacokinetic disposition in animal and man. Diurnal variation in heart and pulse rate was best described with a single cosine function in both dog and man. Canine and human heart rate change were described by a linear model with free drug slope 1.76 bpm microM(-1)[95% confidence interval (CI) 1.17, 2.35] in the dog and 0.76 bpm microM(-1) (95% CI 0.54, 1.14) in man.
Conclusions: The preclinical translational of concentration-response has been described and the potential for further interspecies extrapolation and optimization of clinical trial design is addressed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848407 | PMC |
| http://dx.doi.org/10.1111/j.1365-2125.2009.03594.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A negative relationship between first-pass pulmonary vein isolation and body mass index in ablation index-guided pulmonary vein isolation.
Heart Rhythm O2
December 2024
Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Background: We previously reported the relationship between first-pass pulmonary vein isolation (FPI) and pulmonary vein isolation (PVI) durability in ablation index-guided atrial fibrillation ablation. Obesity is a worsening factor for atrial tachyarrhythmia (AT) recurrence. However, the impact of obesity on FPI has been scarcely reported.
View Article and Find Full Text PDFA proposed algorithm for management of patients with left bundle branch block post-TAVR: 1-year follow-up.
Heart Rhythm O2
December 2024
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Background: Transcatheter aortic valve replacement (TAVR) has revolutionized the management of aortic stenosis and has become the standard of care across a broad spectrum of patients with aortic stenosis. However, it is still associated with high incidence of conduction abnormalities, particularly new left bundle branch block (LBBB). Management of these patients remains a challenge.
View Article and Find Full Text PDFThirty-day unplanned readmissions following hospitalization for atrial fibrillation in a tertiary Syrian center: A real-world observational cohort study.
Heart Rhythm O2
December 2024
Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
Background: Atrial fibrillation (AF) is the most common arrhythmia worldwide. Data regarding 30-day readmission following index admission for AF in the developing world are poorly described.
Objectives: The study aimed to assess the rate, predictors, and trends of 30-day readmission after index admission for AF in Syria.
Risk of stroke with reduced dose direct oral anticoagulants vs standard dose anticoagulation after cardioversion of atrial fibrillation: A systematic review and meta-analysis.
Heart Rhythm O2
December 2024
Cardiology Department, Health Sciences North Research Institute, Northern Ontario School of Medicine University, Sudbury, Ontario, Canada.
Background: There is consensus on the safety of standard dose direct oral anticoagulants (DOACs) for stroke prevention in patients undergoing cardioversion of atrial fibrillation (AF), but outcomes of reduced dose DOACs in this setting remain unclear.
Objective: This systematic review and meta-analysis aimed to compare the rate of cardioversion-associated thromboembolic events between patients taking reduced dose DOACs and those receiving standard dose anticoagulation.
Methods: A systematic search was conducted for studies published between January 1, 2009, and February 16, 2024 in PubMed, Embase, and Cochrane Central Register of Controlled Trials.
Ventricular tachycardia ablation across age groups: Outcomes, trends and demographics. Insights from the National Inpatient Sample Database.
Heart Rhythm O2
December 2024
Department of Cardiology, Geisinger Medical Center, Danville, Pennsylvania.
Background: Ventricular tachycardia ablation (VTA) is an important treatment option for ventricular tachycardia, with increasing use across all age groups. However, age-related differences in outcomes remain a concern.
Objective: This study aimed to investigate age-related trends in VTA procedures and their associated adverse events across the United States from 2011 to 2021.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!