Steady state verapamil tissue distribution in the dog: differing tissue accumulation.
Plasma, heart, and extracardiac tissue verapamil concentrations were measured after sustained intravenous infusions in 11 dogs to determine the differential tissue accumulation of verapamil. A steady state verapamil concentration of 327 +/- 50 ng/ml decreased the mean arterial blood pressure from 104 +/- 9 to 90 +/- 6 mm Hg (p = 0.08) and the P-R interval increased from 118 +/- 4 to 176 +/- 13 ms (p less than 0.001) with second-degree atrioventricular block developing in 6 animals. Verapamil accumulated in organs in the following order: Lung much greater than kidney greater than spleen greater than ventricular myocardium = liver greater than atrial myocardium greater than cerebral cortex greater than fat = skeletal muscle. Levels in the ventricular free wall were consistently greater than atrial levels, but no difference was observed between left versus right-sided cardiac chambers. In summary, affinity of different organs for verapamil is highly variable and organ-specific; furthermore, differential intracardiac chamber accumulation occurs.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D014018:Tissue Distribution; D014700:Verapamil / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
C016904:norverapamil; D014700:Verapamil