Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH

Besides its well known endocrinological effects, thyrotropin-releasing horm one (TRH) has potential clinical value in the treatment of neurotrauma and various neurologic and psychiatric disorders. The aim of this study was to assess if transdermal delivery of TRH and its analogue, M-TRH, in the prese nce of enhancers, is an effective means for administration of the peptides. Using the in vitro diffusion cell method, the effect of ethanol and a terp ene on the transdermal penetration of the peptides across full-thickness ra t skin were studied. Steady-state permeability values fur TRH and M-TRH wer e 8.7 +/- 2.2 and 6.7 +/- 1.4 mug/cm(2) h, respectively. The addition of 3% terpene in combination with 47% ethanol increased the penetration of TRH a nd M-TRH to 16.2 +/- 1.7 and 14.6 +/- 2.1 mug/cm(2) h, respectively. Rats w ere studied in vivo for release of thyroid-stimulating hormone (TSH) as a b iologic effect after transdermally delivered peptide. Topical application o f TRH and M-TRH induced an increase in TSH serum concentration from 0.32 +/ - 0.09 ng/ml to 32.6 +/- 5.0 and 22.9 +/- 7.6 ng/ml, respectively, after 30 min. The addition of terpene and ethanol in combination with TRH or M-TRH, increased the TSH release to 43.0 +/- 3.8 and 48.4 +/- 4.0 ng/ml, respecti vely. It is concluded that, in the rat, peptides can be absorbed through th e sl;in with retained biologic activity, and in amounts sufficient to elici t a physiological response. (C) 2001 Elsevier Science Inc. All rights reser ved.