Background And Relevant Pharmacokinetics

l-glutamine (L-GIn) is a conditionally essential amino acid found in all life forms and the most abundant amino acid in the human body. During conditions of metabolic stress characterised by catabolism and negative nitrogen balance such as trauma (including surgical trauma), prolonged stress, glucocorticoid use, excessive exercise, starvation, infection, sepsis, cancer and severe burns the body is unable to synthesis L-GIn in sufficient quantities to meet biological needs and it becomes essential to have an exogenous intake (Miller 1999, PDRHealth 2006a).

l-glutamine is absorbed from the lumen of the small intestine by active transport (Meng et al 2003) and is then transported to the liver via the portal circulation and enters systemic circulation where it is distributed to various tissues and transported into cells via an active process. Elimination occurs via glomerular filtration and it is almost completely reabsorbed by the renal tubules. Some metabolism of L-GIn takes place in the enterocytes and hepatocytes and it is involved in various metabolic activities, including the synthesis of l-glutamate (catalysed by glutaminase), proteins, glutathione, pyrimidine and purine nucleotides and amino sugars. l-glutamate is converted to l-glutamine by glutamine synthase in the presence of ammonia, ATP and magnesium or manganese.

l-glutamine is predominantly synthesised and stored in skeletal muscles where it comprises around 60% of the free amino acids and makes up 4-5% of muscle protein. In times of metabolic stress, glutamine is released into circulation and transported to tissues in need (Kohlmeier 2003, Miller 1999, PDRHealth 2006a).

Unfortunately L-GIn is not very soluble or stable in solution, especially upon heating for sterilisation, and as a result, until recently, was not included in TPN. The more soluble and stable glutamine dipeptides are now commonly used as the delivery forms in TPN solutions and some nutritional supplements (Kohlmeier 2003,

PDRHealth 2000b). L-Glutamine 610

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