Subcutaneous immunotherapy is an effective treatment for allergy. It works by helping to re-balance an individual’s immune response to allergens and the ability to drive an antibody titre response is greatly improved by the use of adjuvants, the most common being aluminium hydroxide. No data or pre-clinical model on the localisation kinetics of aluminium after subcutaneous injection, based on allergy formulations, currently exists.
METHODS
Albino rats of the Crl:WI(Han) strain each received a single subcutaneous administration on 4 occasions with a 3 or 4 day intervals of a Birch concentrate formulated with either Alhydrogel or L-Tyrosine as the representative depot adjuvant. Dose sites were extracted and digested up to 6 months after final administration and aluminium (Al3+) analysed via ICP-MS.
RESULTS
A significant proportion of aluminium (~50%) was retained at the injection site 3 months post final injection. The rate of clearance of aluminium from the dose site was calculated over a 6 month time period. As an estimate (from D14 and D180 data), the terminal half-life for clearance from SC dose site would be approx 240 days (i.e. time taken to remove half of the dose). Therefore, estimated time to clear 95% dose from SC site would take approx 1.2 years in the rat model.
CONCLUSIONS
The localisation kinetics of aluminium after subcutaneous injection, based on allergy formulation, has been investigated with the rate of clearance of aluminium from the injection site calculated from a rat model. Granuloma formations are one of the most common unwanted adverse reactions when a patient receives allergy subcutaneous immunotherapy. The results presented herein support current understanding that aluminium has the propensity to form focal accumulations in the body, beginning at the site of administration.