Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

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Citation

Hard ML, Mills RJ, Sadler BM, Turncliff RZ, Citrome L

Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

J Clin Psychopharmacol. 2017 Jun;37(3):289-295. doi: 10.1097/JCP.0000000000000691.

PubMed ID
28350572 [ View in PubMed
]
Abstract

BACKGROUND: Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. METHODS: Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. FINDINGS: The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441-882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. CONCLUSIONS: This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.

DrugBank Data that Cites this Article

Drug Reactions
Reaction
Details
Drug Interactions
DrugsInteraction
Apalutamide
Aripiprazole lauroxil
The serum concentration of aripiprazole, an active metabolite of Apalutamide, can be decreased when used in combination with Aripiprazole lauroxil.
Aripiprazole
Aldesleukin
The metabolism of Aripiprazole can be decreased when combined with Aldesleukin.
Aripiprazole
Octreotide
The metabolism of Aripiprazole can be decreased when combined with Octreotide.
Aripiprazole
Fluconazole
The metabolism of Aripiprazole can be decreased when combined with Fluconazole.
Aripiprazole
Diethylstilbestrol
The metabolism of Aripiprazole can be decreased when combined with Diethylstilbestrol.