INTRANASAL ADMINISTRATION OF CALCITONIN AND OF OTHER PEPTIDES - STUDIES WITH DIFFERENT PROMOTERS

Peptide hormones can only be administered by the injective route, not by the oral route: injective therapy has several drawbacks, being non physiologic, poorly reproducible and with a poor patient compliance over prolonged treatments. This explains the interest for alternative routes of peptide administration, in particular for the intranasal route. Intranasal administration of peptides with a short molecule (10 amino acids or less) is now routinely performed in the clinical setting, although their bioavailability is low. In order to be absorbed through the nasal mucosa peptides like insulin, glucagon, GHRH and CRH require the presence of substances, called surfactants or promoters. Salmon calcitonin (sCT) is readily absorbed and shows appreciable metabolic effects and clinical efficacy, with a clear dose-effect ratio both in normal subjects and in post-menopausal women: some data also show a similar effect of sCT and carbicalcitonin. Human calcitonin (hCT) has a lower biological efficacy than sCT and is poorly absorbed: various promoters allow significant nasal absorption and preliminary data show a significant clinical efficacy of hCT thus administered. Also glucagon is absorbed through the nasal mucosa only in the presence of promoters and exerts clear metabolic effects in patients with hypoglycaemia. Surfactants are potentially toxic, so that new approaches are required: poor solubility and polymerization might be responsible for poor nasal absorption: however, cyclodextrins that enhance solubility, were without effect on absorption of glucagon: similarly, monomeric insulin was not absorbed in the absence of promoters. At present, the use of promoters seems justified only for peptides with a poor spontaneous absorption. © 1990.