Effects Of 2% Pilocarpine Membrane With Sodium Hyaluronate On Intraocular Pressure In Rabbits With Ocular Hypertension

[Objective]To evaluate the effects of 2%pilocarpine membrane with sodium hyaluronate on intraocular pressure(IOP) in rabbits with carbomer-induced elevation of IOP,and to study the ocular pharmacokinetics of pilocarpine membrane with sodium hyaluronate in the aqueous humor of rabbit eyes by the method of HPLC.[Methods]Forty-eight New Zealand rabbits were divided into 2 groups randomly,each consisting of 24 animals.One group received 2%pilocarpine membrane with sodium hyaluronate,the other group received 2%pilocarpine hydrochloride eye drop.The aqueous humor was withdrawn from rabbits respectively at 0.5,1,3,6,12,24,48 and 72 h after instillation.The drug was analyzed by high pressure liquid chromatography(HPLC).Left eyes of 18 rabbits were used as control eyes,and their right eyes as model eyes.The ocular hypertension was induced by injection 3g/L carbomer into anterior chamber of the model eyes and paracentesis was performed in the control eyes but without the injection of carbomer. The IOP was measured three days before injection and twice a week in three successive weeks after injection.Eighteen rabbit eyes with carbomer-induced elevation of IOP were randomly divided into 3 groups.Negative control group received sterile saline solution,positive control group received 2%pilocarpine hydrochloride eye drop and test groups received 2%pilocarpine membrane with sodium hyaluronate.The IOP was measured at time intervals of 1,2,3,4,6,12,22,24,32,40,48,56,63 and 72 h after receiving drugs.[Results]In the first part of the experiment,the pilocarpine membrane with sodium hyaluronate group has higher aqueous humor concentration than the pilocarpine hydrochloride eye drop group at any time points measured(P＜0.05),according to the linear calibration curve obtained by HPLC.Measurable amounts of drug were still observed at 48h in the membrane group.The IOP of model eyes,in the second part of the experiment,was 43.50±0.15mmHg,and significantly higher than that of control eyes 12.03±0.08mmHg(P＜0.001).At the beginning,IOP was no difference in three groups including eighteen model eyes.After received drug,the reduction in IOP lasted for 48h in the hypertensive eyes treated by test group;there was significantly difference compared with those of negative control group.The maximum reduction in IOP,however,was significantly different between the test group and the positive control group (P＜0.05).[Conclusion]The detection of IOP proves that the ocular hypertension induced by intrachamber injection 3g/L carbomer in rabbit is a stable ocular hypertension model.In this study,the results indicate that the duration of action of 2%pilocarpine membrane with sodium hyaluronate for lowering IOP is longer than that of 2%pilocarpine hydrochloride eye drop.A single dose of 2% pilocarpine membrane with sodium hyaluronate,which improves the bioavailability and prolongs the duration of action,can reduce IOP for 48h.