The adjuvant effect of oxytocin on GnRH analogue buserelin.

The mucosa of the nasal cavity has relatively high premeability for peptides. Because of the digestive peptidase activity of the gut, the nasal pathway is currently the route of choice for nonparenteral administration of many peptides including gonadotropin releasing hormone analogues (GnRH-a) . Nevertheless, the transmucosal route of administration may have some problems. Variations exist from patient to patient in the absorption of GnRH-a and is also related to the molecular size and hydrophitic/tipophilic characteristics of the individual analogue. Thus, we are confronted with the problem of failure to maintain estradiol suppression despite careful use in few patients receiving intranasal buserelin in our clinic. The low permeability ofpeptidepenneationandmaded mucosal peptidase activity within the nasal mucosa complemented the use of suitable absorption adjuvants. With this regard special interest has been focussed on inhibitors of peptidase activity which am located in the mucus itself or on/within the mucosal cells. Based on a hypothesis that oxytocinand GnRH-a are degradedthrough the same enzymes in the nasal mucosa and in the hypothalamus, we evaluated the use of oxytocin in combination with buserelin both intranasally in two patients who were found to respond poorly to use of intranasal buserelin alone.