Modification of ocular permeability of peptide drugs by absorption promoters.
The purpose of this study was to investigate the effect of absorption promoters on the ocular membrane permeability of thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) as model peptides. The permeabilities of TRH and LHRH were measured using a two-chamber glass diffusion cell mounted with isolated ocular membranes of albino rabbits. Saponin, EDTA, benzalkonium chloride and paraben were used as absorption promoters. These promoters enhanced the permeability of hydrophilic molecules through the cornea and conjunctiva. The promoting effects of the absorption promoters on the conjunctival drug penetrations were not as strong as those on the corneal penetrations. The different responses of the corneal and conjunctival drug penetrations to these promoters may be useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled drugs. The promotional effects of absorption promoters on the corneal drug penetration apparently increased with an increase in penetrant molecular weights, although those on the conjunctival drug penetrations did not depend on the molecular weights.
Sasaki
H
H
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan. sasaki@nagasaki-u.ac.jp
Yamamura
K
K
Mukai
T
T
Nishida
K
K
Nakamura
J
J
Nakashima
M
M
Ichikawa
M
M
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000493:pharmacokinetics*; D008297:Male; D009883:Ophthalmic Solutions; D010226:Parabens / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000493:pharmacokinetics*
D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D012503:Saponins; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D004492:Edetic Acid