Pharmacokinetics and safety of deltoid or gluteal injection of aripiprazole lauroxil NanoCrystal^® Dispersion used for initiation of the long-acting antipsychotic aripiprazole lauroxil

Abstract

Background: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia in adults, can be started with either 21 days of daily oral aripiprazole supplementation or a 1-day initiation regimen consisting of a single injection of a NanoCrystal® Dispersion formulation of AL (ALNCD) and a single dose of 30 mg oral aripiprazole. This phase I study assessed the pharmacokinetics and safety of deltoid versus gluteal ALNCD injections. Methods: Patients with schizophrenia or schizoaffective disorder ( N = 47) were randomized 1:1 to receive a single intramuscular dose of ALNCD in the deltoid or gluteal muscle. Plasma samples were collected over 85 days to measure ALNCD concentration by injection site. Relative aripiprazole bioavailability for deltoid versus gluteal injection was assessed based on area under the curve (AUC∞ and AUClast) and maximum concentration (Cmax) values. Adverse events were monitored throughout the study. Results: Plasma aripiprazole concentrations after a single ALNCD injection were comparable between deltoid and gluteal administration. Mean maximum plasma aripiprazole concentrations were 196.1 ng/ml (deltoid) and 175.0 ng/ml (gluteal). Exposure to aripiprazole was similar, with mean AUC∞ values of 6591 day × ng/ml for deltoid and 6437 day × ng/ml for gluteal. Aripiprazole bioavailability was not significantly different between injection sites. ALNCD administration in the deltoid or gluteal muscle was well tolerated, with similar safety profiles at both sites. Conclusion: ALNCD demonstrated similar exposure and safety profiles between the two administration sites, suggesting that ALNCD can be given in either the gluteal or the deltoid muscles as a component of the 1-day initiation regimen for AL.

Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

“…Aripiprazole lauroxil (AL) Three randomized studies assessed pharmacokinetic profiles after single injections of AL and two studies applied multiple injections. As described previously, higher peak plasma concentrations were found following administration to the deltoid site when compared with the gluteal site (Hard et al 2019;Schoretsanitis et al 2021).…”

Long-acting injectable antipsychotics: what, when, and how

“…32 Aripiprazole containing formulations Table 4 outlines the three different formulations available that contain aripiprazole, with one of them (aripiprazole lauroxil nanocrystal dispersion) reserved for the initiation of aripiprazole lauroxil. 20,[40][41][42][43][44][45][46] Principal differences between the formulations include approved indications, dosage forms/strengths, reconstitution requirements, injection sites, needle gauge/length, injection volume, injection interval, requirement for oral supplementation, concomitant use instructions with CYP3A4 inducers, and instructions for early or late dosing.…”

“…Initiation of aripiprazole lauroxil requires either 21 days of supplementation with oral aripiprazole or the use of the aripiprazole lauroxil nanocrystal dispersion (ALNCD) formulation, available since 2018. 41,42,45,46 ALNCD contains nanometer-sized particles instead of the micrometer-sized particles contained in standard aripiprazole lauroxil; the smaller particles have faster dissolution properties when injected into the muscle. 42 An injection of the ALNCD formulation into either the deltoid or gluteal muscle, plus administration of oral aripiprazole 30 mg that same day, can substitute for the 21 days of oral supplementation that would otherwise be required when starting aripiprazole lauroxil.…”

“…41,42,45,46 ALNCD contains nanometer-sized particles instead of the micrometer-sized particles contained in standard aripiprazole lauroxil; the smaller particles have faster dissolution properties when injected into the muscle. 42 An injection of the ALNCD formulation into either the deltoid or gluteal muscle, plus administration of oral aripiprazole 30 mg that same day, can substitute for the 21 days of oral supplementation that would otherwise be required when starting aripiprazole lauroxil. 46 The first injection of standard aripiprazole lauroxil may be administered on the same day as the ALNCD formulation or up to 10 days thereafter.…”

Plasmatic Levels and Response to Variable Doses of Monthly Aripiprazole and Three-Month Paliperidone in Patients with Severe Schizophrenia. Treatment Adherence, Effectiveness, Tolerability, and Safety

“…Regarding LAI paliperidone, the effective dose found was 120–150 mg. 62–64 Several studies found higher peak PLs after administration in the deltoid than in the gluteal. 41 , 65 Although some studies showed a correlation between dose and PLs with both ARI and AOM, 58 , 66 , 67 the evidence of a clear relationship between LAI PLs effectiveness and side effects is scarce, 66 , 67 which It does not mean that it does not exist. 68 , 69 In general, it is considered unlikely that high levels of SGA-LAI improve response, but also that they increase adverse effects.…”