Comparison of topical and intravenous administration of WIN 55-212-2 in normotensive rabbits.
OBJECTIVE
This study compares the effect of topical versus intravenous (IV) administration of synthetic WIN 55-212-2 (WIN) or timolol on intraocular pressure (IOP).


METHODS
WIN or timolol were administered either topically or by IV in normotensive New Zealand white rabbits. IOP was measured at baseline and 30, 60, and 120 min after administration (n = 4 per group). Blood pressure (BP) and heart rate (HR) were measured concomitantly with IOP.


RESULTS
IV administration of 0.1 mg/kg WIN reduced IOP by 30% after 30 min, which continued to decline for up to 120 min. Timolol injection (25 mu g/kg) also reduced IOP by 25% after 30 min but was not sustained. In comparison, both topical WIN (1.0%) and timolol (0.5%) reduced IOP by 20% from baseline after 30 min. IV injection of either WIN or timolol significantly reduced HR to 155.4 +/- 11.4 bpm and 165.9 +/- 11.1 bpm, respectively, from a baseline of 256.3 +/- 9.9 bpm. Topical administration was well tolerated and did not affect behavior, BP, or HR.


CONCLUSIONS
Topical administration of either WIN or timolol did not decrease IOP as much as IV administration, but the lack of systemic or local toxicity could make it the safer alternative.
Samudre
Sandeep S
SS
Eastern Virginia Medical School, Norfolk, Virginia 23501, USA. sandeepsamudre@gmail.com
Schneider
Jennifer L
JL
Oltmanns
Matthew H
MH
Hosseini
Alireza
A
Pratap
Kiran
K
Loose-Thurman
Patricia
P
Allen
Robert C
RC
Williams
Patricia B
PB
Lattanzio
Frank A
FA
Sheppard
John D
JD
D000287:Administration, Topical; D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002186:Cannabinoids / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects*; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D009281:Naphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D011817:Rabbits; D013999:Timolol / Q000008:administration & dosage; D014065:Tonometry, Ocular
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013999:Timolol