Ocular pharmacokinetics of carnosine 5% eye drops following topical application in rabbit.
OBJECTIVE
To evaluated the ocular pharmacokinetics of carnosine (CAR, a biologically active dipeptide which occurs naturally throughout the human body) 5% eye drops following topical application.


METHODS
CAR 5% eye drops were topically applied repeatedly (50 μL × 4) at an interval of 5 min. Aqueous humor and lens were collected after 5, 15, 30, 45, 60, 90, 120, 150, and 180 min. CAR concentration was determined by high performance liquid chromatography-tandem quadrupole mass spectrometer (HPLC-MS/MS).


RESULTS
CAR concentration in treated eyes was significantly higher than control eyes. Peak concentration (C(max)) of carnosine in treated aqueous humor occurred 60 min following topical administration, with the administrated concentration (total-endogenous concentration) of 40.9 ± 18.9 μg/mL. The area under the concentration-time curve between 0 and 180 min (AUC(0-180)) was 3,276.8 (μg/mL) × min. CAR concentration in treated lens rises to effective level rapidly and changes slightly with time after topical administration. The administrated concentration of car in lens at the last time point (180 min, 1.92 ± 1.65 μg/mL) was not significantly different with the highest value (15 min, 2.11 ± 1.83 μg/mL).


CONCLUSIONS
CAR 5% eye drops were likely to be absorbed into aqueous humor efficiently and accumulated in lens. More attention should be put onto enhancing the penetration of CAR into lens capsule.
Tianyang
Zhou
Z
Henan Eye Institute, Zhengzhou University, Zhengzhou, People's Republic of China.
Ling
Zhu
Z
Liya
Wang
W
Junjie
Zhang
Z
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002336:Carnosine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005123:Eye / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D009883:Ophthalmic Solutions; D009994:Osmolar Concentration; D011817:Rabbits; D013997:Time Factors
D009883:Ophthalmic Solutions; D002336:Carnosine