Pharmaceutical proteins, measuring protein

Hageman et al. [3.13] calculated the absorption isotherms for recombinant bovine somatotropin (rbSt) and found 5-8 g of water in 100 g of protein, which was not only on the surface but also inside the protein molecule. Costantino et al. [3.72] estimated the water monolayer M0 (g/100 g dry protein) for various pharmaceutical proteins and for their combination with 50 wt% trehalose or mannitol as excipient. They compared three methods of calculating MQ (1) theoretical (th) from the strongly water binding residues, (2) from conventional adsorption isotherm measurements (ai) and (3) from gravimetric sorption analysis (gsa) performed with a microbalance in a humidity-controlled atmosphere. Table 3.5 summarizes the results for three proteins. The methods described can be helpful for evaluating RM data in protein formulations. 

Table 1 shows a realistic overview of the successes of CADD in the pharmaceutical industry. Target proteins have been vigorously explored as indicated by the number of structures in the PDB. The only criteria of success that can be used in this situation is to measure compounds put into clinical trials, since about 80% of candidate drugs fail in clinical trials many of these compounds may not end up on the market. 

The volume is divided into five sections. Part one looks at the experimental study of membrane permeability and oral absorption. In Part two, problems of measuring and prediction solubility, as one of the key determinants in the absorption process, will be discussed in detail. In the next part, progress in the science around transporter proteins and gut wall metabolism and their effect on the overall absorption process is presented. Part four looks at the in silico approaches and models to predict permeability, absorption and bioavailability. In the last part of the book, a number of drug development issues will be highlighted, which could have an important impact of the overall delivery strategies for oral pharmaceutical products. 

The upshot of these points is that it may not be practical to follow established guidelines for ADME evaluation. Binding proteins, immunoreactive metabolites and antibodies could interfere with the immunoassays used to measure the activity of biotechnologically derived pharmaceuticals. The link between immunoreactivity and... 

Taylor, S. and Harker, A. (2006) Modification of the ultrafiltration technique to overcome solubility and nonspecificbinding challenges associated with the measurement of plasma protein binding of corticosteroids. Journal of Pharmaceutical and Biomedical Analysis, 41, 299-303. 

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