NASAL ADMINISTRATION OF AN ACTH(4-9) PEPTIDE ANALOG WITH DIMETHYL-BETA-CYCLODEXTRIN AS AN ABSORPTION ENHANCER - PHARMACOKINETICS AND DYNAMICS

1 The systemic absorption and the neurotrophic effect of the metabolic ally stabilized ACTH (4-9) analogue, Org2766, were investigated follow ing intranasal (i.n.) administration. 2 Without additives the nasal bi oavailability of the peptide was in the order of 15 and 10% in rats an d rabbits, respectively. The absorption could be improved by addition of a variety of absorption enhancers to the nasal preparation. The bet a-cyclodextrin derivative, dimethyl-beta-cyclodextrin (DMbetaCD) at a concentration of 5% (w/v) improved the absorption in rats about 5 fold from 13 +/- 4% (mean +/- s.d.) for administration of the peptide alon e to 65 +/= 21%, and in rabbits 1 to 2 fold, from 10 +/- 6% to 17 +/- 8%. 3 The increased permeability of the rat nasal mucosa for Org2766 c aused by DMbetaCD in rats reversed substantially within 1 h. However, the nasal absorption had not yet completely returned to the level with out enhancer. 4 S.c. administered Org2766 accelerated the functional r ecovery from peripheral nerve damage in rats. However, the peptide did not facilitate nerve repair following i.n. administration with DMbeta CD, in spite of the fact that Org2766 was well absorbed. I.v. injectio n of Org2766 was also ineffective.