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Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia.
Schizophr Res. 2014 Nov; 159(2-3):404-10.SR

Abstract

Aripiprazole lauroxil is a linker lipid ester of aripiprazole for extended-release intramuscular (IM) injection. This multicenter, randomized, open-label study evaluated the pharmacokinetics (PK), relative bioavailability, and tolerability of a single IM deltoid or gluteal injection of aripiprazole lauroxil in adult subjects with chronic stable schizophrenia or schizoaffective disorder. Forty-six subjects were randomized 1:1 to aripiprazole lauroxil 441 mg IM in the deltoid or gluteal muscle. Samples were collected through 89 days post-dose to measure levels of aripiprazole lauroxil, N-hydroxymethyl aripiprazole, aripiprazole, and dehydro-aripiprazole. Forty-three (93.5%) subjects completed all study assessments; most were CYP2D6 extensive or immediate metabolizers (96%); two (4%) were poor metabolizers. The PK of aripiprazole following aripiprazole lauroxil was characterized by a steady rise in plasma concentrations (Tmax 44-50 days), a broad peak, and prolonged exposure attributable to the dissolution of aripiprazole lauroxil and formation rate-limited elimination of aripiprazole (t1/2=15.4-19.2 days). Deltoid vs. gluteal administration resulted in slightly higher Cmax aripiprazole concentrations [1.31 (1.02, 1.67); GMR 90% CI]; total exposure (AUCinf) was similar between sites of administration [0.84 (0.57, 1.24)]. N-hydroxymethyl-aripiprazole and dehydro-aripiprazole exposures were 10% and 33-36%, respectively, of aripiprazole exposure following aripiprazole lauroxil. The most common adverse events were injection site pain in 20 subjects (43.5%) and headache in 6 subjects (13.0%) of mild intensity occurring at a similar rate with deltoid and gluteal administration. Exposure ranges with deltoid and gluteal administration overlapped, suggesting that these sites may be used interchangeably. Despite a higher incidence of adverse events, deltoid muscle provides a more accessible injection site and could facilitate patient acceptance.

Authors+Show Affiliations

Alkermes, Inc., Waltham, MA, USA. Electronic address: ryan.turncliff@alkermes.com.Alkermes, Inc., Waltham, MA, USA.Alkermes, Inc., Waltham, MA, USA.Alkermes, Inc., Waltham, MA, USA.Alkermes, Inc., Waltham, MA, USA.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25266547

Citation

Turncliff, Ryan, et al. "Relative Bioavailability and Safety of Aripiprazole Lauroxil, a Novel Once-monthly, Long-acting Injectable Atypical Antipsychotic, Following Deltoid and Gluteal Administration in Adult Subjects With Schizophrenia." Schizophrenia Research, vol. 159, no. 2-3, 2014, pp. 404-10.
Turncliff R, Hard M, Du Y, et al. Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia. Schizophr Res. 2014;159(2-3):404-10.
Turncliff, R., Hard, M., Du, Y., Risinger, R., & Ehrich, E. W. (2014). Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia. Schizophrenia Research, 159(2-3), 404-10. https://doi.org/10.1016/j.schres.2014.09.021
Turncliff R, et al. Relative Bioavailability and Safety of Aripiprazole Lauroxil, a Novel Once-monthly, Long-acting Injectable Atypical Antipsychotic, Following Deltoid and Gluteal Administration in Adult Subjects With Schizophrenia. Schizophr Res. 2014;159(2-3):404-10. PubMed PMID: 25266547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia. AU - Turncliff,Ryan, AU - Hard,Marjie, AU - Du,Yangchun, AU - Risinger,Robert, AU - Ehrich,Elliot W, Y1 - 2014/09/27/ PY - 2014/06/25/received PY - 2014/09/05/revised PY - 2014/09/08/accepted PY - 2014/10/1/entrez PY - 2014/10/1/pubmed PY - 2015/8/20/medline KW - Aripiprazole KW - Aripiprazole lauroxil KW - Atypical antipsychotic KW - Deltoid KW - Gluteal KW - Long-acting injectable KW - Schizophrenia SP - 404 EP - 10 JF - Schizophrenia research JO - Schizophr Res VL - 159 IS - 2-3 N2 - Aripiprazole lauroxil is a linker lipid ester of aripiprazole for extended-release intramuscular (IM) injection. This multicenter, randomized, open-label study evaluated the pharmacokinetics (PK), relative bioavailability, and tolerability of a single IM deltoid or gluteal injection of aripiprazole lauroxil in adult subjects with chronic stable schizophrenia or schizoaffective disorder. Forty-six subjects were randomized 1:1 to aripiprazole lauroxil 441 mg IM in the deltoid or gluteal muscle. Samples were collected through 89 days post-dose to measure levels of aripiprazole lauroxil, N-hydroxymethyl aripiprazole, aripiprazole, and dehydro-aripiprazole. Forty-three (93.5%) subjects completed all study assessments; most were CYP2D6 extensive or immediate metabolizers (96%); two (4%) were poor metabolizers. The PK of aripiprazole following aripiprazole lauroxil was characterized by a steady rise in plasma concentrations (Tmax 44-50 days), a broad peak, and prolonged exposure attributable to the dissolution of aripiprazole lauroxil and formation rate-limited elimination of aripiprazole (t1/2=15.4-19.2 days). Deltoid vs. gluteal administration resulted in slightly higher Cmax aripiprazole concentrations [1.31 (1.02, 1.67); GMR 90% CI]; total exposure (AUCinf) was similar between sites of administration [0.84 (0.57, 1.24)]. N-hydroxymethyl-aripiprazole and dehydro-aripiprazole exposures were 10% and 33-36%, respectively, of aripiprazole exposure following aripiprazole lauroxil. The most common adverse events were injection site pain in 20 subjects (43.5%) and headache in 6 subjects (13.0%) of mild intensity occurring at a similar rate with deltoid and gluteal administration. Exposure ranges with deltoid and gluteal administration overlapped, suggesting that these sites may be used interchangeably. Despite a higher incidence of adverse events, deltoid muscle provides a more accessible injection site and could facilitate patient acceptance. SN - 1573-2509 UR - https://www.unboundmedicine.com/medline/citation/25266547/Relative_bioavailability_and_safety_of_aripiprazole_lauroxil_a_novel_once_monthly_long_acting_injectable_atypical_antipsychotic_following_deltoid_and_gluteal_administration_in_adult_subjects_with_schizophrenia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0920-9964(14)00506-4 DB - PRIME DP - Unbound Medicine ER -