Administration routes peptides/proteins

Many studies have been carried out regarding the absorption of peptides and proteins after pulmonary drug dehvery. The perspectives of a non-parenteral route of administration for larger proteins led to studies on the pulmonary absorption of proteins of different size. To date, over 30 different proteins have been evaluated with regard to absorption rate and... 

Therapeutic peptides, proteins, and peptidomimetics are getting increasingly important. These compounds are degraded in the first instance by luminally secreted and brush border membrane-bound proteases. Because of their hydrophilic character and comparatively large size, they are usually uptaken via the paracellular route after oral administration. 

As mentioned above, the rectal route is very attractive for systemic delivery of peptide and protein drugs, but rectal administration of peptides often results in very low bioavailability due to not only poor membrane penetration characteristics (transport barrier) but also due to hydrolysis of peptides by digestive enzymes of the GI tract (enzymatic barrier). Of these two barriers, the latter is of greater importance for certain unstable small peptides, as these peptides, unless they have been degraded by various proteases, can be transported across the intestinal membrane. Therefore, the use of protease inhibitors is one of the most promising approaches to overcome the delivery problems of these peptides and proteins. Many compounds have been used as protease inhibitors for improving the stability of various peptides and proteins. These include aprotinin, trypsin inhibitors, bacitracin, puromycin, bestatin, and bile salts such as NaCC and are frequently used with absorption enhancers for improvement in rectal absorption. 

There is no doubt that the nasal route of administration of peptide and protein drugs is one of the most attractive alternatives to injections because of its convenience, which should assure good compliance by patients. The pharmacokinetic profile of peptide and protein drugs after nasal administration shows the occurrence of quick absorption and can be tailored, in some cases, by formulation approaches. This also may have therapeutic advantages. 

The respiratory system provides a route of entry into the body for a variety of airborne substances but is also a route of medication. The large contact area of its surfaces extends to more than 30 m. The surfaces have been described as gossamer-thin membranes that separate the lung air from the blood, which courses through some 2000 km of capillaries in the lungs. There is consequently an exquisite degree of intimacy between the lung tissue and blood and the atmospheric environment. The route is thus used for rapid relief of asthmatic conditions, where both local and systemic effects are required, for chronic therapy and for the administration of peptides and proteins. 

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... 

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