LackofaPharmacokineticInteractionbetweenDimebon(Latrepirdine) andDigoxininHealthySubjects

3because digoxin is a narrow therapeutic index drug commonly prescribed to elderly patients for the treatment of heart failure and atrial fibrillation. Furthermore, many clinically significant drug-drug interactions occur with digoxin via inhibition of P-glycoprotein (P-gp)-mediated clearance; therefore, digoxin is also recommended by the FDA 4 as a probe P-gp multidrug resistance 1 (MDR1) substrate to evaluate the potential of a new chemical entity for inhibiting P-gp-mediated clearance. • The effects of dimebon on the clinical pharmacokinetic (PK), urinary excretion, and safety of a sensitive P-gp substrate, such as digoxin, are unknown. The aim of this Phase 1 study was to evaluate the potential drug-drug interaction of dimebon with digoxin in healthy subjects. The interaction was assessed at steady-state plasma concentrations for both drugs, when P-gp inhibition was expected to be maximal. The dosing regimen for digoxin was 0.125 mg once daily (QD) for 14 days; this commercially available tablet strength was selected for safety considerations, and is a commonly prescribed dose in elderly patients.