PHARMACOKINETIC MODELLING OF DIGOXIN AND THEOPHYLLINE: EFFECT OF VOLUME OF DISTRIBUTION AND PLASMA CONCENTRATION

ABSTRACT:
This study explores the pharmacokinetic relationship between volume of distribution (Vd), plasma concentration, and maintenance dose for two drugs with narrow therapeutic indices: digoxin and theophylline at constant bioavailability, half-life of elimination, and dosing interval. Using three-dimensional surface plots, the effect of Vd and plasma concentration on the maintenance dose of digoxin and theophylline was analysed. For digoxin, the plot demonstrates that a larger Vd necessitates a higher maintenance dose to achieve therapeutic plasma levels, essential for treating conditions such as heart failure and arrhythmias. Similarly, for theophylline, which is commonly used to manage asthma and chronic obstructive pulmonary disease, the interaction between Vd and plasma concentration affects the required maintenance dose. These findings highlight the importance of individualized dosing strategies, considering pharmacokinetic properties of each drug, to ensure efficacy and minimize toxicity. The visualized models offer valuable insights for clinical dosing adjustments based on patient-specific factors such as body composition and organ function, which can significantly influence the distribution and clearance of these drugs.
Keywords: Pharmacokinetics, Digoxin, Theophylline, Volume of Distribution, Plasma Concentration, Maintenance Dose