Pharmacokinetics of Der p 2 Allergen and Derived Monomeric Allergoid in Allergic Volunteers

Abstract

Background: Presently, sublingual immunotherapy is widely used as an alternative to the injection route for respiratory allergy, but its pharmacokinetics in humans is poorly known, and data are available only for Par j 1 allergen. We aimed at assessing the biodistribution of iodine-123-radiolabelled Der p 2 in allergic volunteers. Methods: Purified Der p 2 and its monomeric allergoid were radiolabelled with iodine-123 and administered sublingually to 7 allergic volunteers. The subjects were allowed to swallow 6 min after administration. Dynamic (up to 10 min) and static scintigraphic images (30 min, 1, 2, 3 and 20 h) were recorded, and blood samples were obtained at different time points to measure the plasma radioactivity and to assess the presence of circulating radiolabelled species by gel chromatography. Results: The local pharmacokinetics did not differ between allergen and allergoid. Plasma radioactivity began to increase only after swallowing and peaked at 1–2 h. Both the allergen and the allergoid persisted in the mouth for several hours, and traces could be detectable up to 20 h. At radioactivity plasma peak, gel chromatography showed that a fraction of the allergoid, but not the allergen, was absorbed as an intact molecule. Conclusions: These results indicate that the pharmacokinetics of sublingual administration is independent of the allergen used and characterized by the long persistence in the mouth. The contribution of enteric absorption of the allergoid in the mechanism of action of sublingual immunotherapy remains to be defined.

Specific Immunotherapy and Central Immune System

“…The capture and the inflammatory activity on the site of the administration of the therapeutic extract evidenced a very precocious activity that subdue in relatively high values throughout the experiment. These results are consistent with previously described dynamic studies (Bagnasco et al, 2005). The quantitative analysis does not evidence an increase of the local activity as seen in the majority of patients submitted to injectable extracts.…”

“…The same Italian group responsible for the study with allergens administrated by noninjectable routes prompt the question of whether the results obtained up until that moment were restricted to specific characteristics of Parietaria judaica. Following this, the group published another study using a major allergen from Dermatophagoides pteronyssinus, the Der p 2 (Bagnasco, 2005). For the 7 patients with allergic rhinitis, the results were analogous to the ones mentioned above.…”

“…It is not possible to define and characterize the migrating population that focalizes in the distinct structures in patients under SLIT. Despite this, the available scientific knowledge allows us to assume that the allergenic persistence in the sublingual mucosa, as previously demonstrated (Bagnasco et al, 2005), allows the induction of the following immune response. As previously described, abundant lymphoid structures with specific biologic characteristics are present in this mucosa.…”

“…Paradoxically, the characteristics of the DCs present in the oral mucosa, mainly from the plasmacytoid type, are responsible for a less effective response (Novak et al, 2004). Previous work evidenced the presence of the allergenic extract in the sublingual mucosa long after it was swallowed, but it was extremely reduced 24 hours after that administration (Bagnasco et al, 2005). This difference, relatively to the subcutaneous administration, has natural implications in the periodicity of the therapeutical application.…”

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma

“…This reflects the finding that plasma levels of intact HDM allergen remain below detection limits after sublingual administration [36][37][38]. Upon sublingual administration, allergen is presumably taken up by dendritic cells, particularly Langerhans cells, of the oral mucosa and presented to other cells of the immune system [20,39,40].…”