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[PMID]: | 28950271 |
[Au] Autor: | Ohashi-Doi K; Kito H; Du W; Nakazawa H; Ipsen H; Gudmann P; Lund K |
[Ad] Endereço: | Torii Pharmaceutical Co. Ltd., Tokyo, Japan. |
[Ti] Título: | Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation. |
[So] Source: | Int Arch Allergy Immunol;174(1):26-34, 2017. | [Is] ISSN: | 1423-0097 |
[Cp] País de publicação: | Switzerland |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. METHODS: The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. RESULTS: The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. CONCLUSIONS: SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. |
[Mh] Termos MeSH primário: |
Proteínas de Artrópodes/farmacocinética Cisteína Endopeptidases/farmacocinética Imunoterapia Sublingual/métodos
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[Mh] Termos MeSH secundário: |
Administração Sublingual Animais Antígenos de Dermatophagoides/imunologia Proteínas de Artrópodes/imunologia Disponibilidade Biológica Cisteína Endopeptidases/imunologia Seres Humanos Pyroglyphidae/imunologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antigens, Dermatophagoides); 0 (Arthropod Proteins); 0 (Dermatophagoides farinae antigen f 2); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (Dermatophagoides farinae antigen f 1); EC 3.4.22.- (Dermatophagoides pteronyssinus antigen p 1) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171031 |
[Lr] Data última revisão:
| 171031 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170927 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1159/000479693 |
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