Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes.
OBJECTIVE
The aim of this study was to evaluate the pharmacokinetic absorption profiles of two commercially available ophthalmic solutions following a single instillation into each eye of New Zealand white rabbit eyes.


METHODS
A single dose of either timolol maleate with potassium sorbate (TLA) or timolol hemihydrate (THH) was instilled into each eye of New Zealand white rabbits (15 rabbits/drug preparation, 50-microL dose). Animals were euthanized 15, 30, 60, 120, and 180 min after instillation, with 3 animals/drug/time intervals. Aqueous humor from both eyes of each animal was pooled and analyzed for timolol concentration, using the high-performance liquid chromatography method.


RESULTS
TLA reached a mean peak concentration of 3.705 +/- 0.3012 microg/mL at 15 min, tapering to 0.539 +/- 0.1431 microg/mL by 180 min. THH reached a mean peak concentration of 2.239 +/- 0.1430 microg/mL at 15 min postinstillation, tapering to 0.148 +/- 0.0282 microg/mL by 180 min.


CONCLUSIONS
TLA containing potassium sorbate demonstrated an absorption profile of more rapid absorption (1.7 fold greater at 15 minutes) and longer residences time (3.6 fold greater at 180 minutes) than the THH. At every time point throughout the study, TLA demonstrated greater drug concentration than THH.
Baklayan
George A
GA
ISTA Pharmaceuticals, Inc., Irvine, CA, USA. gbaklayan@istavision.com
Collins
Erin C
EC
Thetford
Tim
T
Soriano
Arnel
A
Song
Clara K
CK
Han
John
J
D000042:Absorption; D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D005260:Female; D009883:Ophthalmic Solutions; D010539:Permeability; D011817:Rabbits; D013011:Sorbic Acid; D013810:Therapeutic Equivalency; D013999:Timolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D013999:Timolol; D013011:Sorbic Acid