Biomaterial Database

Myocardial uptake of encainide and its two major metabolites, O-demethyl encainide and 3-methoxy-O-demethyl encainide, in the dog. 1984

R Latini, and A M Gillis, and R E Kates

Encainide is a new antiarrhythmic agent which is currently undergoing clinical evaluation. Two metabolites, O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide (MODE), have been identified. We have investigated the myocardial accumulation of these three compounds in an anesthetized open-chested dog model. We also considered the degree of plasma protein binding and the oil/water partitioning characteristics of these three compounds to see if they explained differences in myocardial accumulation. Each compound was administered by intravenous infusion to a group of five dogs. Blood and myocardial biopsy samplings were carried out under steady-state conditions. The myocardial/plasma concentration ratios for encainide, ODE, and MODE were 8.4, 5.4, and 4.8, respectively. The ratios were compared with a completely randomized analysis of variance followed by multiple comparisons. The myocardial/plasma concentration ratio for encainide was significantly greater (p less than .05) than the ratios of the metabolites; however, the difference between ODE and MODE was not significant. Myocardial uptake of encainide, ODE, and MODE was quite rapid, and the myocardial concentration-time course of each compound followed its time course in plasma closely. Encainide and its two metabolites are only moderately bound to plasma proteins. The mean (+/- SD) percent bound for encainide, ODE, and MODE are 49 +/- 10, 55 +/- 19, 44 +/- 18, respectively. The whole blood/plasma concentration ratios are 1.04 +/- 0.16, 1.08 +/- 0.23, and 1.06 +/- 0.08 for encainide, ODE, and MODE, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D004562	Electrocardiography	Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY.	12-Lead ECG,12-Lead EKG,12-Lead Electrocardiography,Cardiography,ECG,EKG,Electrocardiogram,Electrocardiograph,12 Lead ECG,12 Lead EKG,12 Lead Electrocardiography,12-Lead ECGs,12-Lead EKGs,12-Lead Electrocardiographies,Cardiographies,ECG, 12-Lead,EKG, 12-Lead,Electrocardiograms,Electrocardiographies, 12-Lead,Electrocardiographs,Electrocardiography, 12-Lead
D005260	Female		Females
D000813	Anilides	Any aromatic amide obtained by acylation of aniline.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000889	Anti-Arrhythmia Agents	Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.	Anti-Arrhythmia Agent,Anti-Arrhythmia Drug,Anti-Arrhythmic,Antiarrhythmia Agent,Antiarrhythmia Drug,Antiarrhythmic Drug,Antifibrillatory Agent,Antifibrillatory Agents,Cardiac Depressant,Cardiac Depressants,Myocardial Depressant,Myocardial Depressants,Anti-Arrhythmia Drugs,Anti-Arrhythmics,Antiarrhythmia Agents,Antiarrhythmia Drugs,Antiarrhythmic Drugs,Agent, Anti-Arrhythmia,Agent, Antiarrhythmia,Agent, Antifibrillatory,Agents, Anti-Arrhythmia,Agents, Antiarrhythmia,Agents, Antifibrillatory,Anti Arrhythmia Agent,Anti Arrhythmia Agents,Anti Arrhythmia Drug,Anti Arrhythmia Drugs,Anti Arrhythmic,Anti Arrhythmics,Depressant, Cardiac,Depressant, Myocardial,Depressants, Cardiac,Depressants, Myocardial,Drug, Anti-Arrhythmia,Drug, Antiarrhythmia,Drug, Antiarrhythmic,Drugs, Anti-Arrhythmia,Drugs, Antiarrhythmia,Drugs, Antiarrhythmic