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

• Published in: Schizophrenia research Vol. 159; no. 2-3; pp. 404 - 410
• Main Authors: Turncliff, Ryan, Hard, Marjie, Du, Yangchun, Risinger, Robert, Ehrich, Elliot W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2014; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacokinetics; Aripiprazole; Aripiprazole lauroxil; Atypical antipsychotic; Biological and medical sciences; Biological Availability; Buttocks; Delayed-Action Preparations; Deltoid; Deltoid Muscle - drug effects; Female; Gluteal; Humans; Injections, Intramuscular; Long-acting injectable; Male; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - pharmacokinetics; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Quinolones - administration & dosage; Quinolones - adverse effects; Quinolones - pharmacokinetics; Schizophrenia; Schizophrenia - drug therapy; Young Adult; Gluteal; Aripiprazole lauroxil; Atypical antipsychotic; Deltoid; Schizophrenia; Long-acting injectable; Aripiprazole; Human; 5-HT2A serotonin receptor; Partial agonist; Controlled release form; Neuroleptic; Psychotropic; Quinolinone derivatives; Bioavailability; Psychosis; D2 Dopamine receptor; 5-HT1A Serotonine receptor; Dosage form; Adult; Antagonist; Safety
• ISSN: 0920-9964; 1573-2509; 1573-2509
• DOI: 10.1016/j.schres.2014.09.021

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 441mg IM in the deltoid or gluteal muscle. Samples were collected through 89days 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 44–50days), a broad peak, and prolonged exposure attributable to the dissolution of aripiprazole lauroxil and formation rate-limited elimination of aripiprazole (t1/2=15.4–19.2days). 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.