Strattera (Atomoxetine) Half-Life
Strattera has an elimination half-life of approximately 5 hours in extensive metabolizers and 24 hours in poor metabolizers of CYP2D6. 1
Half-Life by CYP2D6 Metabolizer Status
Extensive Metabolizers (EMs)
- Mean elimination half-life: 5.2 hours 1
- Represents approximately 93% of Caucasians and 98% of African Americans 1
- Mean apparent plasma clearance: 0.35 L/hr/kg 1
Poor Metabolizers (PMs)
- Mean elimination half-life: 21.6 hours 1
- Represents approximately 7% of Caucasians and 2% of African Americans 1
- Mean apparent plasma clearance: 0.03 L/hr/kg (10-fold lower than EMs) 1
- Results in approximately 10-fold higher AUC and 5-fold higher peak plasma concentrations compared to extensive metabolizers 1
Clinical Implications of Half-Life Differences
Dosing Considerations
- Poor metabolizers require significantly lower doses due to the prolonged half-life and substantially reduced clearance 1, 2
- Upon multiple dosing, plasma accumulation occurs in poor metabolizers but minimal accumulation in extensive metabolizers 3
- Laboratory tests are available to identify CYP2D6 poor metabolizers for dose optimization 1, 2
Drug Interactions Affecting Half-Life
- Potent CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) convert extensive metabolizers to a poor metabolizer phenotype, resulting in approximately 10-fold increase in AUC and 5-fold increase in peak concentrations 1, 4
- When co-administered with fluoxetine, atomoxetine clearance is markedly reduced, necessitating dose adjustment 4, 1
Duration of Action vs. Half-Life
- Despite the relatively short 5-hour half-life in extensive metabolizers, single-dose atomoxetine provides 24-hour efficacy, likely due to neuroadaptive changes at the norepinephrine transporter 5
- This dissociation between plasma half-life and clinical effect duration allows for once-daily dosing in both metabolizer phenotypes 6, 5