Continuous monitoring of circadian variations in intraocular pressure by telemetry system throughout a 12-week treatment with timolol maleate in rabbits.
OBJECTIVE
The aim of this study was to examine the effect of a 12-week treatment with two formulations of timolol maleate on the amplitude of the circadian fluctuation in intraocular pressure (IOP).


METHODS
Conscious Japanese White rabbits housed under a controlled 12-hour light-dark cycle were used. IOP was measured by a telemetry system. Each animal was treated topically for 12 weeks with 0.5% timolol solution (TM) twice-daily, 0.5% timolol gel-forming solution (TM-gel) once-daily, or saline twice-daily, and the circadian variation in IOP was measured every week.


RESULTS
Administration of TM or TM-gel did not change IOP in the light phase, but significantly reduced it in the dark phase in each of the 12 weeks. The IOP reductions at 2 h after administration in the TM and TM-gel groups over the 12 weeks were, respectively, 3.6 +/- 0.3 mmHg and 3.4 +/- 0.2 mmHg versus the Saline group. The amplitudes of the circadian fluctuations in IOP in the TM group in weeks 3, 6, and 12 were 15%, 15%, and 18% smaller than those in the Saline group, while the corresponding values for the TM-gel group were 18%, 16%, and 19%, respectively.


CONCLUSIONS
TM-gel administered once-daily was as effective at lowering IOP as TM administrated twice-daily over the 12-week experimental period. This study reveals that, in rabbits, both formulations of the timolol maleate induced significant IOP reductions in the dark phase and decreased the amplitudes of the circadian fluctuations in IOP for 12 successive weeks.
Akaishi
Takahiro
T
Glaucoma Group, Research and Development Center, Santen Pharmaceutical Co., Ltd., Nara, Japan. takahiro.akaishi@santen.co.jp
Ishida
Naruhiro
N
Shimazaki
Atsushi
A
Hara
Hideaki
H
Kuwayama
Yasuaki
Y
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D007322:Instillation, Drug; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D013686:Telemetry; D013997:Time Factors; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D013999:Timolol