比较国产与进口复方噻吗洛尔滴眼液对家兔瞳孔和眼压的影响

目的 :比较复方噻吗洛尔国产滴眼液 (含0 .5 %噻吗洛尔和 2 %硝酸毛果芸香碱 )和进口滴眼液 (含 0 .5 %噻吗洛尔和 2 %盐酸毛果芸香碱 )对家兔瞳孔和眼压的影响。方法 :测量正常家兔瞳孔直径变化 ,制备水负荷高眼压兔模型并用压陷式眼压计测量家兔眼压。结果 :国产和进口滴眼液在给药后 15～ 12 0min ,家兔瞳孔明显缩小 ,较对照组眼压明显下降 ,2组间无显著统计差异。结论 :含不同毛果芸香碱盐基的复方噻吗洛尔国产滴眼液与进口滴眼液均具有明显缩瞳和降眼压作用 ,其药理作用强度和作用持续时间无明显差异。     

Effect of latanoprost/timolol and dorzolamide/tiomolol on intraocular pressure after phacoemulsification surgery

AIM: To evalaute the effect of fixed-combination latanoprost 0.005%/timolol maleate 0.5% and dorzolamide hydrochloride 2%/timolol maleate 0.5% on postoperative intraocular pressure after phacoemulsification cataract surgery. METHODS: This study is a prospective, randomized, double-masked and placebo-controlled. The study included 90 eyes of 90 patients which were scheduled to have phacoemulsification surgery. Patients were randomly assigned preoperatively to 1 of 3 groups (30 eyes of 30 patients). Two hour before surgery, the patients received one drop latanoprost/timolol (group 1), dorzolamide/timolol (group 2) and placebo (group 3, control group). The IOPs were measured at preoperative and postoperative 4, 8, and 24 hours. RESULTS: The preoperative mean intraocular pressure was not statistically significant between both drug groups and control group. In group 1 and 2, the postoperative mean IOP [group1: (14.03±3.15)mmHg and group 2: (14.16±4.43)mmHg] at 24 hours were significantly lower than the control group [(16.93±3.70)mmHg, (P<0.05)]. In addition, the postoperative mean IOP of group 1 [(14.90±3.69)mmHg] at 8 hours was significantly lower than the control group [(17.70±3.89)mmHg, (P<0.05)], but there was no significant difference between group 2 [(16.16±5.23)mmHg] and control group at 8 hours (P>0.05). CONCLUSION: When compared with placebo, the use of preoperative fixed combination of latanoprost/ timolol and dorzolamide/timolol is an effective method for preventing intraocular pressure elevation in 24 hours after phacoemulsification surgery, but did not completely prevent IOP spikes.     

益精补阳还五汤联合马来酸噻吗洛尔治疗POAG的疗效分析

目的:探讨益精补阳还五汤联合马来酸噻吗洛尔滴眼液对原发性开角型青光眼(POAG)患者眼血供、眼压及视力的影响。方法:选取2018-02/2020-02本院POAG患者120例,依据随机表分为滴眼组(60例,给予马来酸噻吗洛尔滴眼液治疗)和汤液组(60例,给予马来酸噻吗洛尔滴眼液联合益精补阳还五汤治疗),比较两组眼血供[视网膜中央动脉(CRA)和睫状后动脉(PCA)的舒张末期血流速度(EDV)、收缩期峰值血流速度(PSA)、阻力指数(RI)]、眼压、视力、视野[平均视敏度(MS)、平均视野缺损(MD)]、疗效、不良反应。结果:汤液组和滴眼组治疗后CRA和PCA的EDV、PSA及视力、MS明显高于治疗前,汤液组和滴眼组治疗后CRA、PCA的RI及眼压、MD明显低于治疗前,汤液组治疗后CRA和PCA的EDV、PSA及视力、MS明显高于滴眼组,汤液组治疗后CRA、PCA的RI及眼压、MD明显低于滴眼组(P<0.05);汤液组治疗有效率明显高于滴眼组(P<0.05);汤液组和滴眼组不良反应率无差异(P>0.05)。结论:益精补阳还五汤联合马来酸噻吗洛尔滴眼液可有效改善POAG患者眼血供、眼压及视力、视野,提高了疗效,且安全性好。     

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma

Introduction: Medical therapy of glaucoma aims to maintain the patient’s visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence.

Areas covered: The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®).

Expert opinion: The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.     

马来酸噻吗洛尔透皮贴剂的制备及释药机理研究

 目的：制备马来酸噻吗洛尔透皮贴剂，研究其释药机理。方法：利用双室渗透扩散装置，进行离体皮肤体外渗透实验，通过改变扩散液的pH值及皮肤的状态，研究其释药机理。结果：马来酸噻吗洛尔贴剂的体外释药方程为：Q=207.6t^l/2-176.1(r=0.997),24 h累积释药量为845.6 μg/cm2。随着扩散液pH升高，药物的渗透系数逐渐增大，去除角质层皮肤对药物渗透系数远远大于完整皮肤，且完整皮肤的贮库效应大于去除角质层皮肤。结论：马来酸噻吗洛尔主要以分子型透过皮肤，在经皮渗透过程中存在贮库效应，渗透的主要屏障为角质层。     

The role of clinical drug trial methodology with respect to studies of new drugs. Clinical trials of timolol

The use of the Randomized Clinical Trial (RCT) to assess the safety and efficacy of a new drug or treatment can provide a clear evaluation of the relative benefits and risks of the new therapy as compared to the longer-established treatment methodology. In some cases, such as insulin, the benefits are immediately apparent; in other cases, such as photocoagulation for proliferative diabetic retinopathy, the consensus is not so easily obtained, and the clinical trial can supply the answer. Furthermore, the RCT provides the opportunity to identify adverse reactions, in particular those which present with a seemingly unrelated or unexpected set of symptoms. In conducting clinical trials of timolol, researchers must be alert for beta-adrenergic antagonist effects, such as were seen with practolol, and should be especially careful to note early, mild reactions which may be the forerunners of later, more severe or irreversible adverse effects.     

A fluorophotometric study of the effect of topical timolol on aqueous humor dynamics

A modification of the fluorophotometric method of Jones and Maurice is described and used to measure the aqueous flow coefficient. The method was used to measure the effect of topical timolol on aqueous humor dynamics in 15 human subjects. It was found that the acute decrease in intraocular pressure caused by timolol can be explained entirely by its effect on the aqueous flow. The mean aqueous flow coefficient in the timolol treated eye was found to be 0·0126 min^?1 before timolol, and 0·0067 min^?1 after timolol. A small effect on the aqueous flow coefficient of the untreated eye was also observed.     

Iontophoretic in Vivo Transdermal Delivery of β-Blockers in Hairless Rats and Reduced Skin Irritation by Liposomal Formulation

Purpose. To demonstrate the in vivo transdermal delivery and establish the comparative pharmacokinetics of five -blockers in hairless rat. Methods. Intravenous dosing was initially done via jugular cannula. For iontophoretic delivery, current (0.1 mA/cm²) was applied for 2 h through a drug reservoir patch containing the -blocker (10 mg/ml). Blood samples were collected and analyzed by stereoselective HPLC assays. Any irritation resulting from patch application was quantified by a chromameter. Multilamellar liposomal formulation was prepared by the thin-film hydration method and converted to unilamellar liposomes by extrusion. Results. With transdermal iontophoresis, therapeutically relevant amounts of propranolol (83.78 ± 7.4 ng/ml) were delivered within an hour and lasted for up to 4 h. C_max (185.1 ± 56.8 ng/ml) was reached at hour 3. A significantly higher amount (p < 0.05) of sotalol HCl was delivered compared to other -blockers. There was no significant difference in the S/R ratio of AUC_0-t for enantiomers after both intravenous and transdermal delivery. Skin irritation was significantly reduced (p < 0.05) when a liposomal formulation of the propranolol base was used rather than the base itself. Conclusions. The comparative pharmacokinetics of intravenous and transdermal iontophoretic delivery of five -blockers in hairless rats was established. It was shown that there is no stereoselective permeation.     

Fixed combinations of dorzolamide-timolol and brimonidine-timolol in the management of glaucoma

Importance of the field: The emergence of fixed-combination drugs for the treatment of glaucoma has, to some extent, changed the medical management of glaucoma. The potential benefits of these drugs include a reduction in the total number of drops and preservatives instilled per day and improved patient comfort factors, which may contribute to better compliance. Combination medications may also improve therapeutic efficacy and play an important role in controlling medication cost. However, the fixed dosing may be a disadvantage in some cases.

Area covered in this review: This review describes the composition, pharmacokinetics, mode of action, efficacy, side effects, and safety profile of fixed-combination dorzolamide–timolol and fixed-combination brimonidine–timolol.

What the reader will gain: Understanding of the pros, cons, and safety profile of two FDA approved fixed-combination antiglaucoma medication.

Take home message: Fixed-combination medications may be a reasonable adjunct to prostaglandins if a large drop in the intraocular pressure (IOP) is desired and adding only one medication is unlikely to reach the target IOP range. Both mentioned drugs are effective in reducing the IOP and further clinical studies will help identify differences in efficacy between the two. The clinician must make an individualized assessment of the medication's risk-benefit profile for each patient.     

Effect of timolol on the amplitude and dynamics of accommodation

There is still debate about whether the ciliary muscle is innervated by the sympathetic nervous system. We investigated the amplitude and the dynamics of accommodation under influence of the non-selective beta-blocker timolol. For this purpose the variations in thickness of the human lens during step-like changes in accommodation were measured with high-resolution A-scan echography. Results showed that the dynamics of accommodation, expressed in the time constants of the response, were affected as well as the amplitude.