Evidence for Variable Digoxin Absorption as Estimated by Pharmacological Response Intensities

• Published in: Journal of pharmaceutical sciences 1974-03, Vol.63 (3), p.411-416
• Main Author: Schoenwald, R.D.
• Format: Article
• Language: English
• Subjects: Absorption; Absorption, digoxin—evidence for variability estimated by ventricular rate slowing, doseeffect and response-time curves constructed; Administration, Oral; Digoxin; Digoxin - metabolism; Digoxin - pharmacology; Digoxin, variable absorption—estimated by pharmacological response intensities, dose—effect curves, ventricular rate slowing, response-time curves; digoxin-evidence for variability estimated by ventricular rate slowing; digoxin-evidence suggesting new significance; dose-effect curves; Dose-Response Relationship, Drug; doseeffect and response-time curves constructed; Enterohepatic cycling; Enterohepatic cycling, digoxin—evidence suggesting new significance; Heart Rate - drug effects; Humans; Injections, Intravenous; Intestinal Absorption; Mathematics; Regression Analysis; response-time curves; Time Factors; variable absorption-estimated by pharmacological response intensities; ventricular rate slowing; Ventricular rate slowing-used as pharmacological response intensity parameter for studying variable digoxin absorption
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600630321

A dose-effect curve constructed from ventricular rate slowing and oral maintenance doses for digoxin provided evidence for assuming that occupation theory correctly describes drug-receptor site interaction. From the tenets of occupation theory, response intensities were linearly related to biophasic drug levels and provided the input for bi- and triexponential least-squares fits for an intravenously administered 1.2-mg dose of digoxin to patients hospitalized with auricular fibrillation. A biexponential fit best described biophasic drug levels when the biophase was represented by a peripheral compartment. Intravenous biexponential equation parameters were utilized to perform an absorption analysis following oral dosing of 1.2mg of digoxin to the same patients. From calculations of fractional amounts unabsorbed with time, significant absorption of digoxin was found to be occurring through 24hr at progressively decreasing but noticeably variable rates; absorption was calculated to be 98.7% complete by 120hr. Absorption rates were most rapid over the first 5hr but quite variable thereafter. Oscillations in the intravenous and oral response-time curves, observed between 3 and 12hr following dosing, likewise produced fluctuations in mathematically derived biophasic drug levels, fractional amounts unabsorbed, and absorption rates for the oral dose, suggesting enterohepatic cycling of digoxin to be more significant than previously thought.