Protein administration routes

Due to the lack of activity after oral administration for most peptides and proteins, administration by injection or infusion - that is, by intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration - is frequently the preferred route of delivery for these drug products. In addition, other non-oral administration pathways have been utilized, including nasal, buccal, rectal, vaginal, transder-mal, ocular, or pulmonary drug delivery. Some of these delivery pathways will be discussed in the following sections in the order of the increasing biopharmaceutic challenges to obtain adequate systemic exposure. 

Since the administration routes are mainly parenteral, the formulation has to be injectable. An injectable formulation requires specific excipients, ways of preparation and formulation types liquid, suspension, or solid formulations. In the development of protein drugs, various formulation principles are used. In Table 5, examples of some of the formulation principles are given. 

Name Year Indication Inclusion criteria Proteine/Cene Route of administration Type of trial Follow-up Outcome... 

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). 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

The most widely used parenteral administration avenues are intravenous (iv), intramuscular (im), and subcutaneous (sc). In addition, there are several minor applications (e.g. intraarterial). Application of a protein drug by the different main parenteral administration routes may have profound effects on the pharmacological performances. When the drug is administered iv, it is immediately available for action in the circulation, while drugs administered im or sc need more time to reach the blood (depot effect), and consequently the pharmacokinetic (PK) profiles could be different. Besides the PK, the route of administration may have influence on the primary distribution of the drug. For example, when administered sc, smaller and hydrophiUic proteins tend to enter the venous system, while larger and/or more hydrophobic proteins tend to... 

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