The adjuvant effect of bacitracin on nasal absorption of gonadorelin and buserelin in rats.

Nasal absorption of gonadorelin (luteinizing hormone-releasing hormone; LH-RH) and buserelin, an LH-RH agonist, was studied in anesthetized rats. Administration of peptides was by nasal instillation of aqueous peptide/buffer solutions. Peptide absorption was monitored using different techniques: (a) by specific radioimmunoassays for serum levels of lutropin (LH), (b) by the cumulative urinary excretion of buserelin, and (c) by the ovulatory activity after nasal LH-RH and buserelin, respectively. Without adjuvant the nasal absorption of LH-RH and buserelin was relatively poor compared to subcutaneous or intravenous injection. Using absorption adjuvants of different types, e.g., sodium taurodihydrofusidate (STDHF) and bacitracin, marked increases in nasal absorption and, therefore, significant nasal adjuvant activity were found, as demonstrated by an increase in the biological response after nasal administration of the peptides. The mucosal compatibility of bacitracin at the concentrations used for enhancement of absorption was confirmed by an in vitro investigation using isolated gastric mucosa of guinea pigs as a test model.