title: Corneal critical barrier against the penetration of dexamethasone and lomefloxacin hydrochloride: evaluation by the activation energy for drug partition and diffusion in cornea.
abstract: The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approach to investigate the mechanism of drug permeability.
authors.affiliation: Senju Pharmaceutical Co., LTD. Hiranomachi, Chuo-Ku, Osaka, Japan. yasueda@senju.co.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yasueda
authors.forename: Masayo
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Masazumi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Akiharu
authors.initials: A
authors.lastname: Isowaki
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtori
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001548:Benzalkonium Compounds / Q000494:pharmacology; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004058:Diffusion; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D009883:Ophthalmic Solutions; D010539:Permeability; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D011817:Rabbits; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D001548:Benzalkonium Compounds; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D003907:Dexamethasone; C053091:lomefloxacin