Protein absorption, factors influencing

The impact of formulation on protein absorption and disposition is also an important factor in the development and use of biologic molecules. Stability of the protein drug in subcutaneous or muscle tissues and absorption rates directly influence the overall response. Various physical and chemical approaches are used to stabilize proteins and other macromolecules as a part of optimizing dosage formulations. 

TABLE 13.1. Factors influencing protein and peptide absorption... 

There are two major barriers in the mucosal absorption of peptide and protein—a penetration barrier and an enzymatic barrier (as supported by Lee ), which are relevant to nasal delivery. Taking those into consideration, basic factors influencing the nasal absorption of peptide and protein drugs will be discussed in this section. 

Farr, S.J. Gonda, 1. Licko, V. Physicochemical and physiological factors influencing the effectiveness of inhaled insulin, pulmonary absorption of therapeutic peptides and proteins. In Respiratory Drug Delivery VP, Dalby, R.N., Byron, P.R., Farr, S.J., Eds. Interpharm Press, Inc. Buffalo Grove, IL, 1998 25-33. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

In addition, the solubilized sulfonamides as a group diffuse very widely into the tissues, penetrating into all fluids, including urine, bile, and milk. The degree of tissue penetration is influenced by several factors, including the ionization state and lipophilicity of the particular sulfonamide, the vascularity of the absorption site, and the degree of protein binding. 

Biological factors. The species of animal is a very important factor especially affecting metabolism but also influencing the other phases of disposition. The pH of the gastrointestinal tract, the nature of the skin, and breathing rate all may affect absorption. Plasma proteins and fat can affect distribution. Biliary excretion is affected by species in relation to the molecular weight threshold. 

Limited data are available about the effects of individual dietary components on absorption, and consequently the requirement, of Mn. Dietary protein and phosphorus levels (33), calcium level (34) and the effect of a partial substitution of soy protein for meat (28) have been tested in balance studies without any obvious effect of Mn absorption or retention. However, since the main route of excretion is via the bile, the conventional balance technique is probably not sensitive enough to identify dietary factors that influence Mn absorption. 

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