Plasma protein manufacturing

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Figure B3.1.4 A 15% SDS-pdyacrylamide gel assayed for proteinase inhibitors. (A) Gel stained with Coomassie brilliant blue for total protein. (B) Gel assayed for serine-proteinase inhibitory activity against trypsin. Food-grade proteinase inhibitors used in surimi manufacture were assayed. Lane 1, whey protein concentrate. Lane 2, bovine plasma proteins. Lane 3, egg white. Each lane contains 15 pg protein. Lane M, molecular weight standards. The dark bands in (B) indicate proteins with proteinase inhibitory activity. Numerous proteins in egg white (lane 3) are shown to have inhibitory activity against trypsin. Adapted from Weerasinghe (1995).

The major manufacturing process for plasma-derived products is the fractionation of human plasma, the liquid part of blood, to remove the minute amounts of plasma proteins present in each unit of plasma. To make the process commercially successful, very large quantities of plasma are mixed together and then fractionated. Dr. Elias Cohn developed the initial process in the early 1940s at Harvard University using differential cold alcohol precipitation. Essentially the same process (as modified by Oncley) is used today, with the addition of more rigorous viral inactivation techniques to increase safety. The conditions have been set to both efficiently fractionate the protein and to maximize viral partition, inactivation, or removal. Considering the... 

The liver is responsible for manufacturing many plasma proteins, including albumin, aj-antitrypsin, a-feto protein and prothrombin. The measurement of total plasma protein is of little value in determining liver function, as values may be normal despite disturbances in the production of individual proteins. The two proteins which are of... 

When mammalian red cell Hb is used as the raw material for production of a modified Hb, the requirement for the minimization of plasma proteins and red cell stroma is a rigorous and general one. Some manufacturers meet this requirement by extensive red cell washing to reduce contamination by residual plasma, controlled lysis, and careful filtration of the hemoly-sate, followed by ultrafiltration. Other manufacturers add a chromatographic purification step to this procedure. Published data indicate that the phospholipid content of the so-called stroma-free Hb resulting from either process is very low (<2pg/ml). ... 

The most likely explanation is that azapropazone inhibits the liver enzymes concerned with the metabolism of phenytoin, resulting in its accumulation. It also seems possible that azapropazone displaces phenytoin from its plasma protein binding sites so that levels of unbound (and active) phenytoin are increased. Information seems to be limited to the reports cited, but it appears to be a clinically important interaction. The incidence is uncertain, but an interaction occurred in all 5 of the subjects in the study cited. The manufacturers contraindicate azapropazone in patients taking phenytoin. ... 

Because tacrolimus is extensively bound to plasma proteins, the UK manufacturers mention the possibility of protein-binding interactions with oral... 

In 1989 the International Federation of Clinical Chemistry (IFCC) established a Committee for Plasma Protein Standardization to address this problem by preparing, characterizing and calibrating a new international secondary reference preparation for plasma proteins. Forty thousand 1 ml vials of a lyophilised preparation were produced and calibrated [S.Baud-ner et al, Manufacture and characterization of a new reference preparation for 14 plasma proteins/CRM 470 = RPPHSS Lot 5 J. Clin. Lab. Anal. 8 (1994) 177-lW]. The material was released in 1993, in Europe, by the Community Bureau of Reference of the Commission of the European Communities (BCR) as the Certified Reference Material for Immunochemical Measurements of 14 Human Serum Proteins (CRM 470) and in 1994 in USA by the College of... 

Protein trafficking is the process whereby a protein manufactured within a cell is delivered (trafficked) to its desired location within the cell. In the case of hERG channels, it is the process whereby the relevant proteins are delivered to their locations within the plasma membrane. 

Ultrafiltration is used to separate and concentrate various protein types from foodstuffs, such as whey protein from cheese manufacture, egg albumen, and blood plasma proteins (Porter and Michaels, 1970). Ultrafiltration achieves separation by the use of a semi-permeable membrane. The process is carried out under hydraulic pressure. 

Plasma proteins are manufactured in the liver and their serum levels are reduced when the ability of hepatocytes to synthesize proteins is impaired. The ammonia level rises when hepatocyte damage prevents biosynthesis of amnrania to urea. Bilirubin can increase as a result of either hepatocyte dysfunction or cholestasis. Prothrombin time increases because of the reduced availability of coagulation factors normally synthesized by hepatocytes. Sorbitol dehydrogenase (SDH) is a liver-specific enzyme that is released when... 

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