
	Pharmacokinetics of peptides

Peptides are involved in many nerve or hormone communications and are of particular interest to dis-ciplines such as gastroenterology, neurobiology, cardiology, the study of reproduction and of immunoregulation. Many recently-discovered peptides are potentially useful for therapeutic purposes.

Obtaining many analogues by peptide synthesis has demonstrated the way peptides work and has also made it possible to obtain compounds which may eventually be used as drugs. Modification of certain peptides, in fact, gives them agonistic or antagonistic properties, and also in some cases tissue specificity. One of the principle techniques is to introduce non-natural amino acids to reduce metabolisation and to incorporate lipophilic chains to facilitate passage through the tissues. Thus, although endogenous compounds have an elimination half-life of less than 10 minutes, their analogues show a resistance to elimination that is reflected by half-lives usually longer than 2 hours.

Generally speaking, the cellular distribution of peptides or their analogues reflects their linkage specific-ity and their physico-chemical properties. Metabolisation sites usually correspond to tissue rich in peptidases such as the liver or the kidneys. Their low availability in oral administration has led to the production of new galenic forms, using, for example, cutaneous administration by iontophoresis or inclusion in biodegradable polymers.

Peptides are administered in low doses and have effective plasma concentrations which are often less than one ng/ml. The study of their pharmacokinetic characteristics therefore requires the use of particu-larly sensitive analytical techniques, a condition which is met by immunoassays. The latter must use tracers of high specific activity and must avoid certain traps, such as: interaction of peptides with plasma proteins, presence of similar forms (precursors or metabolites), enzyme degradation in vitro. Sensitive and specific assays have been developed by SPI collaborators for hypothalamic peptides (gonadoliberin, thyroliberin) for neuropeptides (substance P, encephalins) or for certain peptides involved in the regulation of the im-mune system (acetyl-SDKP). E.E.

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