Physiologically Based Pharmacokinetic Modeling to Assess Ritonavir-Digoxin Interactions and Recommendations for Co-Administration Regimens.

backgroundDigoxin is a commonly used cardiac glycoside drug in clinical practice, primarily transported by P-glycoprotein (P-gp) and susceptible to the influence of P-gp inhibitors/inducers. Concurrent administration of ritonavir and digoxin may significantly increase the plasma concentration of digoxin. Due to the narrow therapeutic window of digoxin, combined use may lead to severe toxic effects. PURPOSE: Utilize a Physiology-Based Pharmacokinetic (PBPK) model to simulate and predict the impact of the interaction between ritonavir and digoxin on the pharmacokinetics (PK) of digoxin, and provide recommendations for the combined medication regimen.

methodsUsing PK-Sim

resultsAccording to the model simulations, the steady-state exposure of digoxin increased by 86.5% and 90.2% for oral administration, and 80.2% and 90.2% for intravenous administration, respectively, when 0.25 mg or 0.5 mg of digoxin was administered concurrently with ritonavir. By reducing the dose of digoxin by 45% or doubling the oral administration interval, similar steady-state concentrations can be achieved compared to when the drugs are not co-administered.

conclusionsIn clinical practice, the influence of drug interactions on the plasma concentration changes of digoxin within the body should be considered to ensure the safety and effectiveness of treatment.