The extent to which a drug is glycosylated plays a crucial role in drug/body interactions. Glycoproteins comprise a significant proportion of the total body protein and exhibit two-dimensional electrophoresis patterns that are distinct from those of non-glycosylated proteins. Major subgroups are N-glycosylation, O-glycosylation, and by far the most abundant, O-linked glycosylation3. A glycoprotein will be considered extensively N-glycosylated if about 50% or more of the sugar residues are attached to Asn or Asn/Gln (E) combinations; if one or more sialic acid residues are present; the ratio of negatively charged glycans (mannose and/or galactose) to neutral glycans exceeds 2:1; over 25% of the total number of glycans (both neutral and negative) exhibit an (N-M) Man(9)-5 linkages3.
How a drug is glycosylated can be of great importance, particularly in the manufacture of oral dosage forms. The extent to which a drug or therapeutic protein is glycosylated has been shown to play a crucial role in many aspects of drug body interactions including absorption, metabolism, toxicity and immunogenicity. A better understanding of these gm csf growth factor can enable the rational design and development of oral dosage forms that show physiological patterns of drug concentration within the body.
A glycosylated drug is one that carries carbohydrates. These carbohydrates make drugs less likely to be excreted in the urine and therefore stay in the blood stream longer, affecting their effects and duration of action. Drug-metabolizing enzymes in the blood and tissues can affect whether a drug is administered in a free or a conjugated form, potentially altering its safety profile and pharmacodynamic properties. The intended effect of a drug can also be altered by glycosylation, e.g., some drugs that are intended to remain in the blood need to be destabilized before they metabolize while others are destabilized and cleared from the body before they pass into the blood.
Viral infections, over time, lead to a decrease in the number of white blood cells. This leads to a decrease in the production of interferon-gamma, a protein that is involved in fighting viral infections. A low serum value of Interferon-gamma can mean immune deficiency and increased risk of serious infection. When you come down with a common cold or flu, it is because your body has not produced enough IFN-gamma.
A bioassay for human gamma interferon test measurement was established and validated. Serial twofold dilutions from 100 pg/ml up to 1 ng/ml were performed in duplicate in 96-well assay plates, serum samples diluted in EIA buffer were added. IFN-gamma concentration was interpolated from a fourpoint standard curve for IFN-gamma measured on the bioassay plate by means of an enzymeimmunoassay. Then the lower limit of quantification (LLOQ) as well as the limit of detection (LOD) was determined using undiluted patient sera and compared with the assay measured value. The LLOQ values ranged from 51.7 pg/ml to 87 pg/ml and the LOD values ranged from 23.2 pg/ml to 55.2 pg/ml respectively.
