Ocular pharmacokinetics and availability of topically applied baicalein in rabbits.
OBJECTIVE
To evaluate the ocular pharmacokinetics and availability of baicalein following topical application.


METHODS
Hydroxypropyl beta-cyclodextrin (HP-beta -CD) was used to formulate an aqueous eye drop to improve aqueous solubility of baicalein. A single dose of either baicalein suspension (1%) (Bai-SP) or baicalein (1%)/HP-beta-CD (10%) solution (Bai-CD) was topically applied to rabbits. Aqueous humor and cornea were collected after 5, 10, 20, 30, 45, 60, 90, and 120 min. Baicalein concentrations were determined by high-performance liquid chromatography (HPLC) after extraction.


RESULTS
After topically applying Bai-CD, the baicalein concentrations in aqueous humor were significantly increased at 20-120 min except at 90 min compared with those of Bai-SP (p < 0.05). The highest levels of baicalein in aqueous humor (Cmax, 4.11 +/- 0.75 microg/ml) were obtained after 30 min application of Bai-CD, 3.6 times greater than that corresponding to the Bai-SP at 20 min. The Bai-CD produced an over 2.1-fold bioavailability (AUC(0-120), area under the concentration time curve between 0 and 120 min) increase in aqueous humor compared to the Bai-SP. Peak baicalein concentration in cornea (56.53 +/- 17.02 microg/g) was achieved within 5 min after topical application of Bai-CD and 4.5 times higher than that of Bai-SP at the same timepoint. The baicalein levels in corneas obtained after application of Bai-CD were all much higher than those obtained by Bai-SP (p < 0.01), whereas the drug levels became undetectable 30 min after topical application of Bai-SP.


CONCLUSIONS
Bai-CD formulation is superior to Bai-SP for increasing ocular bioavailability.
Henan Eye Institute, No. 7 Weiwu Road, Zhengzhou, Henan Province 450003, China. chocolate8098@msn.com
Li
L
Zhang
Junjie
J
Zhang
Liya
L
Wang
Huiyun
H
Xia
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D005079:Excipients; D005123:Eye / Q000378:metabolism*; D044950:Flavanones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D009883:Ophthalmic Solutions; D009994:Osmolar Concentration; D011817:Rabbits; D012995:Solubility; D012996:Solutions; D013535:Suspensions; D013997:Time Factors; D047392:beta-Cyclodextrins
D005079:Excipients; D044950:Flavanones; D009883:Ophthalmic Solutions; D012996:Solutions; D013535:Suspensions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C006680:baicalein