Abstract
PurposeLong-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation in the tissue, which has not been well defined in the literature. The purpose of this work is to establish an experimental baseline for describing these responses.MethodsNon-human primates and rodents were used to examine the response to LAI formulations of two clinically relevant atypical antipsychotics, aripiprazole monohydrate and olanzapine pamoate monohydrate.ResultsA foreign body response develops with elevations of key cytokines such as IL-1α, IL-1β, TNFα, and IL6 at the site of injection. However, the tissue response for the two atypical antipsychotics compounds diverge as evidenced by quantitative differences observed in cytokine levels at various time points after dosing.ConclusionsOur studies show that, while the drugs are in the same therapeutic class, the response to each of these compounds can be distinguished qualitatively and quantitatively, supporting the idea that the injection site reaction involves a multiplicity of factors including the properties of the compound and cellular dynamics at the site of injection.
Highlights
The key to optimal efficacy of many drugs is sustained systemic exposure to therapeutic concentrations of the active compound
Long-acting injectables (LAIs) are available for a wide range of medical indications, and interest in this area continues to grow because of LAIs impact on adherence and improved patient outcome [1]
The area of atypical antipsychotics (ATAPs), which are used in the treatment of schizophrenia, bipolar disorder and depression, has seen major advances in recent years including LAIs of important drugs like risperidone, palperidone, olanzapine and aripiprazole [2,3,4,5]
Summary
The key to optimal efficacy of many drugs is sustained systemic exposure to therapeutic concentrations of the active compound. Long-acting injectable (LAI) drug products are designed to provide this prolonged exposure. LAIs are usually delivered either subcutaneously or intramuscularly, enabling slow drug release over an extended period of time [1]. There are a wide variety of approaches used for LAI delivery including microsphere technology, liposomal encapsulation, nanoand microcrystalline dispersions, lipophilic solutions, oil-based emulsions, and implants. The area of atypical antipsychotics (ATAPs), which are used in the treatment of schizophrenia, bipolar disorder and depression, has seen major advances in recent years including LAIs of important drugs like risperidone, palperidone, olanzapine and aripiprazole [2,3,4,5]
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