Novel delivery of antiarrhythmic agents.
Conventional antiarrhythmia therapy by oral or intravenous routes of administration is often ineffective and results in drug-associated complications and toxicity. In addition, poor bioavailability and a high first-pass effect limit therapeutic applications of several investigational antiarrhythmic compounds, which are otherwise more potent and less toxic than available agents. The regional nature of the several cardiac diseases, such as ischaemia, restenosis or heart valve calcification, may require a high concentration of drug at the location of the disease, which by conventional routes may not be attainable due to systemic toxicity of the drug. Localised cardiac delivery of antiarrhythmic agents, based on drug-polymer implants, may have several advantages, including enhanced drug effects and reduced systemic drug toxicity. Computer-assisted automated feedback systems may further enhance the usefulness of this therapy in the clinical setting. Before clinical application of this method of drug delivery further study will be required, but it is hypothesised that pharmacokinetic variability for drugs delivered in this manner will be reduced and therefore efficacy and toxicity will be more predictable.
Labhasetwar
V
V
University of Michigan Medical Center, Division of Pediatric Cardiology, Ann Arbor, USA.
Levy
R J
RJ
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000592:standards; D016503:Drug Delivery Systems; D004343:Drug Implants; D005246:Feedback; D006321:Heart / Q000187:drug effects*; D007478:Iontophoresis; D009206:Myocardium / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants