Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension.
In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body. Intravenous injections of caffeine significantly increased the IOP at 0.25 and 1 hr after a single dose. The ocular hypertension recovered within 2 hr following dosing. Over time, there were no differences in the outflow between the caffeine and control groups. The instillation of befunolol lowered outflow and produced ocular hypotension. The levels of the IOP and outflow in dogs treated with caffeine and befunolol in combination were almost the same as those in dogs treated with befunolol alone. Single-dose and combination-dose studies demonstrate that intravenous caffeine increases the IOP in normal beagle dogs possibly by increasing aqueous humor formation and not by the inhibition of aqueous humor drainage through the trabecular meshwork.
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
K
K
Kurata
H
H
Fujimoto
R
R
Tsukuda
T
T
Suzuki
T
T
Ando
M
M
Tokuriki
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology*; D002110:Caffeine / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D004347:Drug Interactions; D007275:Injections, Intravenous; D007322:Instillation, Drug; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D002110:Caffeine; C006034:befunolol