When is steady state reached for aripiprazole (Abilify) and when should plasma levels be checked?

Steady State Levels for Aripiprazole and Timing for Level Checks

Steady state concentrations of aripiprazole are attained within 14 days of dosing. 1 This is the appropriate time to check plasma levels if therapeutic drug monitoring is needed.

Pharmacokinetic Profile of Aripiprazole

Aripiprazole has distinctive pharmacokinetic properties that determine when steady state is reached:

• Mean elimination half-life: approximately 75 hours for aripiprazole and 94 hours for its active metabolite dehydro-aripiprazole 1
• Steady state concentrations are attained within 14 days of consistent dosing for both active moieties 1, 2
• At steady state, the pharmacokinetics of aripiprazole is dose-proportional 1
• Dehydro-aripiprazole (the main active metabolite) represents about 40% of the parent drug exposure in plasma 1, 3

Timing for Therapeutic Drug Monitoring

When conducting therapeutic drug monitoring (TDM) for aripiprazole:

• Blood should be collected for TDM in steady-state conditions, which is reached after at least 5 drug half-lives following changes in dose 4
• Given aripiprazole's half-life of approximately 75 hours, this translates to waiting at least 14 days after initiating treatment or changing the dose 1, 2
• The appropriate sampling time is immediately before ingestion of the morning dose (trough level), approximately 12-16 hours after the last dose (or 24 hours if given once daily) 4

Factors Affecting Aripiprazole Levels

Several factors can influence aripiprazole plasma concentrations:

• Genetic polymorphism of CYP2D6 enzyme system affects elimination - poor metabolizers have a longer half-life (about 146 hours) 1
• Comedication with CYP3A4 and CYP2D6 inducers or inhibitors can change serum levels by up to 51% 3
• When such medications are added or removed, a new steady state will be reached only after waiting at least 14 days 4

Clinical Implications

• Full therapeutic effect may take 1-2 weeks, and sometimes up to 4 weeks, after reaching steady state 2
• Therapeutic plasma concentration range has been reported between 150-300 ng/ml for optimal improvement with minimal side effects 3
• Dose adjustments should not be made before 2 weeks of continuous therapy to allow reaching steady state 2

Common Pitfalls to Avoid

• Checking levels too early (before 14 days) may lead to misinterpretation of results
• Failing to account for drug interactions that affect aripiprazole metabolism
• Not considering CYP2D6 metabolizer status when interpreting levels
• Overlooking the contribution of the active metabolite dehydro-aripiprazole to the overall clinical effect

Remember that therapeutic drug monitoring should be performed with proper timing to ensure accurate interpretation of results and appropriate clinical decision-making.