Pharmacokinetic analysis of plasma ampreloxetine exposure indicated that the terminal half-life was 30–40 h, reached steady state after 6 days, and accumulated three- to four-fold with once-daily dosing.

Population pharmacokinetic modeling identified sex and smoking status as statistically significant covariates indicating that cytochrome P450 1A2-based metabolism is the key mechanism for ampreloxetine elimination.

Based on the pharmacokinetic/pharmacodynamic relationship, a once-daily ampreloxetine dose of 10 mg is predicted to achieve sustained norepinephrine transporter engagement during the entire dosing interval.