Corneal and scleral permeability of quinolones--a pharmacokinetics study.
OBJECTIVE
To investigate the corneal and scleral permeability of nalidixic acid and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits.


METHODS
The corneal and scleral permeability coefficients of ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using high performance liquid chromatography (HPLC). The aqueous humor levels of norfloxacin and ciprofloxacin were measured separately by topical instillation of 0.3% solutions of the two drugs onto rabbit eyes.


RESULTS
Nalidixic acid had a higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not significantly different (p > 0.1). Comparing the corneal and scleral permeability coefficients, only values for nalidixic acid were not significantly different (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p > 0.05), while all other drugs had scleral permeability coefficients 8 to 10 times greater than corneal permeability coefficients. The mean aqueous humor concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after instillation was around 0.3 microg/mL, a value higher than MIC90 of most bacteria.
Tai
Ming-Cheng
MC
Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Lu
Da-Wen
DW
Chiang
Chiao-Hsi
CH
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002937:Cinoxacin / Q000737:chemistry / Q000494:pharmacology; D002939:Ciprofloxacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003315:Cornea / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D015365:Enoxacin / Q000737:chemistry / Q000494:pharmacology; D009268:Nalidixic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009643:Norfloxacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015242:Ofloxacin / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011817:Rabbits; D012590:Sclera / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014867:Water / Q000378:metabolism
D015363:Quinolones; D014867:Water; D015365:Enoxacin; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D015242:Ofloxacin; D002937:Cinoxacin; D009643:Norfloxacin