Antibodies administration route

Although it is highly likely that the clinical effectiveness of anti-CDlla and anti-ICAM-1 antibodies in EAE will depend upon features of experimental design, e g., method of disease induction, and the stage and route of antibody administration, the overall impression from the current literature is that CD 11a and ICAM-1 are not major participants in the CNS extravasation of lymphocytes. It also appears that anti-L-selectin antibodies do not affect the clinical course of EAE.138... 

In this section, the pharmacokinetics of clinically important peptide/protein drugs, such as insulin, EPO, G-CSF, interferon, growth hormone, leuprolide, desmopressin, and antibodies, are described in relation to their administration routes and formulations (i.e., dosage forms). 

Aprotinin. Aprotinin is a naturally occurring serine protease inhibitor, has found widespread applications either by the intravenous route or as a component of biological sealants, because of its ability to decrease blood loss, and, as a consequence, transfusion requirements. Anaphylactic reactions are mediated by IgG and IgE antibodies. The risk of anaphylactic reactions has been estimated between 0.5 and 5.8% when used intravenously during cardiac surgery, and at 5 for 100,000 applications when used as a biologic sealant [25]. Patients previously treated with this drug present an increased risk and any new administration should be avoided for at least 6 months following an initial exposure [25]. 

No antibody activity was found after oral immunization in any of the individual rabbits immunized with liposphere R32NS 1-vaccine formulation. However, rabbit immunization by all parenteral routes tested resulted in enhanced immunogenicity, with increased antibody IgG levels over the entire postimmunization period. The individual rabbit immune response shows that immunization by subcutaneous injection was the most effective vaccination route among all parenteral routes of administration tested. 

A third consideration is that certain routes of administration may favor immu-nogenicity of recombinant proteins. In early trials, rDNA proteins introduced by subcutaneous or intramuscular injections (procedures known to improve the immu-nogenicity of proteins) resulted in a higher frequency of antibody responses than in the intravenous route. 

In the IV route, anaphylactic reactions (caused by administration of an agent to an animal previously sensitized to it or to a particularly sensitive species such as a guinea pig) may be especially severe, probably because of sudden, massive antigen-antibody reactions. When the drug is given by other routes, its access to antibody molecules is necessarily slower moreover, its further absorption can be retarded or prevented at the first sign of a serious allergic reaction. 

Epstein, J.E., E.J. Gorak, Y. Charoenvit, et al.. Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramus-cular/intradermal routes. Hum Gene Ther, 2002.13(13) 1551-60. 

Immunogenicity may be affected by the route of administration. Extravascular injection has been shown to stimulate antibody formation more than IV application, but this is most likely due to the increased immunogenicity of protein aggregates and precipitates formed at the injection site [44]. A recent study investigated the effect of the route of administration of INF-P preparations on inducing anti-INF-P antibodies in multiple sclerosis patients. The results indicate that IM injections appear less immunogenic compared to SC injections, resulting in both a lower serum level of anti-INF-P antibodies as well as a delay in their appearance [45]. 

Monoclonal antibody Dosea) Dose unit Dosing interval [h] Route of administration C ,axb) lmg/L] tmaxC [h] Fd> [%]... 

Route of administration SC injection has a higher incidence of forming antiidiotype antibodies than IM or IV administration. 

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