Pharmacokinetics of azithromycin and moxifloxacin in human conjunctiva and aqueous humor during and after the approved dosing regimens.
OBJECTIVE
To evaluate the ocular pharmacokinetics of azithromycin and moxifloxacin in human conjunctiva and aqueous humor in subjects undergoing cataract surgery.


METHODS
Multicenter, open-label, randomized study.


METHODS
Subjects scheduled for routine cataract surgery and with normal-appearing conjunctiva were eligible. One conjunctival biopsy sample and 1 aqueous humor sample were obtained from subjects randomly assigned to 1 of 10 prespecified time points (1 to 312 hours) after treatment initiation of azithromycin ophthalmic solution 1% or moxifloxacin ophthalmic solution 0.5%. Samples were assayed using liquid chromatography tandem mass spectrometry.


RESULTS
Azithromycin 1% provided high concentrations (peak level, 559.7 μg/g) in human conjunctiva that were sustained at levels 1 to 2 orders of magnitude higher than those of moxifloxacin 0.5% throughout the 7-day dosing period and for at least 7 days thereafter. Azithromycin also showed an extended half-life (65.7 hours) in conjunctiva relative to that of moxifloxacin (28.6 hours). Accordingly, the concentration of azithromycin was maintained well above the minimum inhibitory concentration required for inhibition of growth of 90% of tested bacterial isolates for at least 7 days, whereas moxifloxacin conjunctival levels fell to levels at or less than the minimum inhibitory concentration required for inhibition of growth of 90% of tested bacterial isolates approximately 24 hours after the last dose. Peak aqueous humor concentration of moxifloxacin was higher (0.77 μg/mL) than that of azithromycin (0.053 μg/mL). No clinically relevant safety findings were observed.


CONCLUSIONS
Azithromycin 1% demonstrated high, therapeutic levels in the conjunctiva that were maintained up to 7 days after completion of a 1-week dosing regimen. Aqueous humor levels, however, were subtherapeutic with this dosing regimen. In comparison, moxifloxacin achieved lower conjunctival tissue levels, but higher aqueous humor levels.
Stewart
William C
WC
PRN Pharmaceutical Research Network, LLC, Charleston, South Carolina, USA.
Crean
Christopher S
CS
Zink
Richard C
RC
Brubaker
Kurt
K
Haque
Reza M
RM
Hwang
David G
DG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001372:Aza Compounds / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000493:pharmacokinetics*; D001682:Biological Availability; D002387:Cataract Extraction; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000378:metabolism*; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D017963:Azithromycin; D000077266:Moxifloxacin