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  • Long-acting atypical antipsychotics: characterization of the local tissue response.

Long-acting atypical antipsychotics: characterization of the local tissue response.

Pharmaceutical research (2014-02-22)
Sara Montminy Paquette, Had Dawit, Magali B Hickey, Elaine Merisko-Liversidge, Orn Almarsson, Daniel R Deaver
ABSTRACT

Long-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. Non-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. A 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. Our 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pamoic acid, ≥97.0% (T)
Aripiprazole, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Aripiprazole, ≥98% (HPLC)
USP
Pamoic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, SAJ first grade, ≥99.0%
Sigma-Aldrich
Dimethyl sulfoxide, JIS special grade, ≥99.0%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.0%, suitable for absorption spectrum analysis
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC
Sigma-Aldrich
Dimethyl sulfoxide solution, 50 wt. % in H2O
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Sigma-Aldrich
Dimethyl sulfoxide, Vetec, reagent grade, 99%
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%