The effect of sodium tauro-24,25-dihydrofusidate on the nasal absorption of human growth hormone in three animal models.
The ability of a novel permeation enhancer, sodium tauro-24,25-dihydrofusidate (STDHF), to increase the systemic delivery of human growth hormone (hGH) after intranasal administration was investigated in rat, rabbit, and sheep. Formulations of hGH with STDHF exhibited greatly enhanced nasal absorption at concentrations of STDHF above its critical micelle concentration. The increase in bioavailability was 11-fold in rats and in rabbits and 21-fold in sheep for formulations containing 0.5% STDHF as compared to those without STDHF. Glycocholate or taurocholate at 0.5% was three to five times less effective than STDHF at enhancing hGH absorption in rats. Additionally, the pulsatile absorption kinetics observed after intranasal delivery more closely resemble the endogenous secretory pattern of hGH than those obtained following subcutaneous administration.
Baldwin
P A
PA
California Biotechnology Inc., Mountain View 94043.
Klingbeil
C K
CK
Grimm
C J
CJ
Longenecker
J P
JP
D000042:Absorption; D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005672:Fusidic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013006:Growth Hormone / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000494:pharmacology
D013501:Surface-Active Agents; D005672:Fusidic Acid; C053824:tauro-24,25-dihydrofusidate; D013006:Growth Hormone