The pharmacodynamics of orally taken verapamil and verapamil retard as judged by their negative dromotropic effects.
The widely recognized, negative dromotropic effects of alpha-isopropyl-alpha-[N-methyl-N-homaveratryl)-gamma-aminopropyl]-3-4-dimethoxyphenylacetonitrile (verapamil, Isoptin) on arterio-venous (A-V) nodal conductions were studied using long-term atrial stimulation (AS) in 7 healthy volunteers whose mean age was 30 years. A control group consisting of three of the volunteers who underwent long-term atrial stimulation without medication was established. Since an isolated, well-known drug effect was studied over a long period of time, it was felt that this was an acceptable method for reaching valid pharmacodynamic conclusions. Atrial stimulation was carried out at hourly intervals up to 14-16 h and continued to the highest possible rate without the occurrence of 2nd degree A-V block before and following oral application of verapamil, 240 mg. The stimulus-Q (S-Q) prolongation at increased pace rates was compared to the control. Verapamil retard was tested in a similar course of investigation the following day. The results clearly demonstrated that both forms of verapamil are effective when taken orally. Verapamil acts 2 h after oral application. The peak effectiveness of the drug is found at 5 h and at this point A-V block can occur at low atrial stimulated rates. The effect of verapamil retard is obvious only after 6 h but is still apparent after 14 h and it remains constant with no peak in effectiveness. Characteristics of the resulting regressions allow to distinguish the effect of verapamil on A-V conduction from influences that might be mediated by the diurnal changes in tone of the autonomic nervous system only. The effect of verapamil after oral application is more pronounced with higher heart rates. The pharmacodnaymics of verapamil evaluated with regard to a single well-known pharmacological effect, have not necessarily to be identical with the pharmacokinetics and the bioavailability of the drug.
D000328:Adult; D000704:Analysis of Variance; D001283:Atrioventricular Node / Q000187:drug effects*; D001682:Biological Availability; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D003864:Depression, Chemical; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006327:Heart Block / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D012044:Regression Analysis; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D014700:Verapamil