Formulation of carteolol chitosomes for ocular delivery: formulation optimization, ex-vivo permeation, and ocular toxicity examination.

Background:Conventional delivery systems like solution and suspension are commonly used for the treatment of ocular diseases but have low corneal residence time and hence the duration of effect is limited. These drawbacks of conventional systems can be reduced by preparing bioadhesive chitosan (CH) coated noisome.Methods: Niosomes (NIM) of carteolol (CT) were developed by the thin-film hydration method and optimised by the Box-Behnken statistical design. Further, the optimised CT-NIM was coated with CH to enhance the ocular residence time . The optimised formulation was evaluated for vesicle size, entrapment efficiency, and in-vitro drug release and transcorneal permeation, histopathology, etc.Results: CT-NIM-opt showed the vesicle size and entrapment efficiency of 235 ± 3.54 nm, and 70.45 ± 0.87%, respectively. DSC spectra exhibited that CT was completely encapsulated into the CH-CT-NIM matrix. Drug release from CH-CT-NIM-opt was more sustained (68.28 ± 4.2%) than CT-NIM (75.69 ± 4.5% in 12 h) and CT solution (99.89 ± 2.8% in 4 h). The CH-CT-NIM-opt represented a strong bio-adhesion (89.76 ± 3.6%) than CT-NIM-opt (15.65 ± 3.4%). The permeation flux exhibited 1.13-fold higher permeation than CT-NIM and 3.23 fold than CT solution. The corneal hydration was found to be within the limit value. The histopathology study exhibited no structural damage to the cornea . HET-CAM results showed zero scores indicating no bleeding or haemorrhage. CH-CT-NIM-opt was found to be isotonic and exhibited good stability when stored at 4 °C for the stated duration of time.Conclusion: The above findings suggested that NIM can be a potential carrier for the delivery of CT with better ocular residence time.

A prospective study of topical carteolol therapy in Chinese infants with superficial infantile hemangioma.

BACKGROUND/OBJECTIVE: To report our observations from a trial of the short-term effectiveness and safety of topical carteolol hydrochloride drops to treat infantile hemangiomas (IHs). METHODS: From October 2012 to September 2015, the study recruited 349 children with superficial IHs. Participants were randomized to two groups: treatment (n = 224 who received 2% carteolol hydrochloride drops administered to the lesion surface twice daily) and observation (n = 125 who did not receive treatment). Therapy duration was 6 months. RESULTS: The mean age at the beginning of treatment was 3.2 months. Treatment responses were categorized as class 1 (total regression), class 2 (partial regression or controlled growth), or class 3 (no response). Of infants receiving carteolol treatment, 10.7% (24 patients) were categorized as class 1, 72.3% (162 patients) as class 2, and 17.0% (38 patients) as class 3. Of infants in the observation group, 5.6% (7 patients) were categorized as class 1, 25.6% (32 patients) as class 2, and 68.8% (86 patients) as class 3. No adverse effects were noted during treatment. CONCLUSION: Carteolol is an effective, safe topical treatment for superficial IHs. Carteolol may be used to treat proliferative superficial IHs, particularly in infants younger than 6 months.

Individualized Treatment for Infantile Hemangioma.

Infantile hemangioma can grow dramatically or typically locate on the face, which may lead to functional impairment, cosmetically disfiguring and exhibiting complications such as ulceration, bleeding, or infection. Early intervention is necessary. In this study, the authors chose individual treatment for different patients. From January 2012 to December 2016, 185 patients with hemangioma were enrolled into this study. Lesion area ranged from 0.5 cm × 0.5 cm to 9 cm × 12 cm. The initial treatment age ranged from 1 to 7 months with an average age of 3.9 months. Thirty-five children achieved the treatment of Intralesional Compound Betamethasone, 134 children achieved the treatment of oral propranolol, and 16 children achieved the treatment of topical carteolol. In the follow-up, the treatment could be repeated or switched to oral propranolol if the tumor tended to grow again. At the end of follow-up, 89% of the patients' tumors shrinked or involuted completely, 5 patients switched to oral propranolol. The adverse effects included soft tissue atrophy, moon face, diarrhea, heart rate reduction, and liver enzyme abnormalities. All of the patients recovered in a short period. Early treatment for hemangioma can achieve good results and avoid functional impairment. For different patients, the authors suggest individualized treatment according to the tumors' size and location.

Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles.

We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect when combined with dissolved carteolol on the bioavailability and intraocular pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5% mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and MH particles. The transcorneal penetration and IOP-reducing effect of carteolol was evaluated in rabbits. The mean particle size of mCMFC was 7.2 µm, and the particle size was reduced to 73.5-113.5 nm by the bead mill treatment. The MH particles in nCMFC remained in the nano size range for 8 days after preparation, and the amounts of lacrimal fluid and corneal damage were unchanged by repetitive instillation of nCMFC (twice a day for 4 weeks). The transcorneal penetration of carteolol was enhanced by the combination with MH nanoparticles, and the IOP-reducing effect of nCMFC was significantly higher than that of CRT-solution or mCMFC. In conclusion, we designed nCMFC, and showed that the high levels of dissolved carteolol can be delivered into the aqueous humor by the instillation of nCMFC. Combination with MH nanoparticles may achieve an enhancement of corneal penetration for water-soluble drugs. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs.

[Effect of 0.004% travoprost and 2% carteolol on intraocular pressure in patients with ocular hypertension after laser peripheral iridotomy or trabeculectomy in primary angle-closure glaucoma].

OBJECTIVE: To compare the intraocular pressure (IOP) lowering effect of 0.004% travoprost and 2% carteolol in patients with ocular hypertension (OHT) after laser peripheral iridotomy (LPI) or trabeculectomy in primary angle-closure glaucoma (PACG). METHODS: Clinical case control trial. 52 consecutive PACG patients (52 eyes) with IOP > 21 mm Hg (1 mm Hg = 0.133 kPa) after LPI or trabeculectomy were enrolled. 24 patients received topical application of 0.004% travoprost (once daily) and 28 received 2% carteolol (twice daily). IOP lowering effect of travoprost and carteolol before and after treatment was measured by Goldmann tonometer and compared using t-test. The relationship of IOP lowering effect and the degree of angle open was performed by gonioscope and analyzed using Spearman rank correlation. RESULTS: Compared with pre-treatment, the IOP was significantly reduced in 24 patients (24 eyes) in 0.004% travoprost group [pre-treatment: (24.67 ± 3.08) mm Hg, post-treatment: (18.58 ± 2.71) mm Hg; t = 6.600, P < 0.05], while significantly reduced in 28 patients (28 eyes) received 2% carteolol [pre-treatment: (23.57 ± 1.60) mm Hg, post-treatment: (19.57 ± 1.60) mm Hg; t = 5.130, P < 0.05]. 0.004% travoprost group is more significant in both quantity and percentage of IOP lowering than 2% carteolol (t = 2.533, 2.532; P < 0.05). There was no correlation between the IOP lowering effect and the degree of angle open in both groups (0.004% travoprost r = 0.145, 0.009; P > 0.05; 2% carteolol r = 0.090, 0.183, P > 0.05). CONCLUSIONS: Both of 0.004% travoprost and 2% carteolol reduce IOP in patients with OHT after LPI or trabeculectomy in PACG. 0.004% travoprost is more effective than 2% carteolol in IOP lowering. However, the decrease of IOP is not acted through the alteration of anterior chamber angle in both study groups.

[Long-acting carteolol hydrochloride 2% ophthalmic solution phase IV study--investigation of the effectiveness, safety and plasma concentration].

PURPOSE: We investigated the effectiveness, safety and plasma concentration of long-acting carteolol hydrochloride 2% ophthalmic solution (LA) as compared with the original carteolol hydrochloride 2% ophthalmic solution(CA). METHODS: Patients with primary open angle glaucoma and ocular hypertension were randomized to 62 patients of LA group (LA once a day) and 62 patients of CA group (CA twice a day) in this multicenter, open-label trial. The intraocular pressure (IOP), pulse rate, blood pressure and plasma concentration were examined for 8 weeks. RESULTS: The IOP reduction and reduction rate were not significant at any point between the two groups. Systolic blood pressure decreased significantly in both groups, however, diastolic blood pressure decreased only in the CA group. The plasma concentration of the LA group was significantly lower than that of the CA group. CONCLUSIONS: The IOP reduction effect of the LA group was the same as the CA group. This study suggests that long-acting treatment with alginic acid can be useful for reducing systemic side effects.

Efficacy and safety of the fixed combinations of tafluprost/timolol and latanoprost/carteolol.

In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.

Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs.

AIM: To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis. METHODS: Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte-colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays. RESULTS: In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group. CONCLUSION: This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis.

[The deleterious effect of certain surface active agents on the ocular surface]. / Les effets délétères de certains collyres sur la surface oculaire.

Most ocular solutions enter the eye through the corneal epithelial barrier. In order to pass through this barrier, these hydrosoluble drugs require to be associated with a detergent agent to increase topical efficiency. Although these agents have a preservative action, it was recently demonstrated that, after short or long term use, toxic side effects on the ocular surface will occur.

[Ocular hypotensive effect of 1% carteolol long-acting eye drops--a double-masked, randomized phase III study in ocular hypertension or primary open-angle glaucoma patients comparing long-acting carteolol eye drops vs. current product].

PURPOSE: To compare the ocular hypotensive activity and safety profile of long-acting 1% carteolol hydrochloride eye drops (long-acting formulation) to those of 1% carteolol hydrochloride eye drops(currently prescribed drug) for reduction of intraocular pressure. SUBJECTS AND METHODS: Patients with primary open-angle glaucoma or ocular hypertension (146 cases) were assigned randomly to the long-acting drug group (74 cases) and the currently-prescribed drug group (72 cases). Long-acting eye drops were instilled once a day in the morning (along with one drop of placebo at night), and currently-prescribed eye drops were instilled twice a day in the morning and at night. Eye drops were administered for 8 weeks. Intraocular pressure was monitored at 2, 4, and 8 weeks after the initiation of drug instillation for evaluation of equivalence. RESULTS: Intraocular pressure was significantly reduced during the entire follow-up period in both groups. In the long-acting drug group, the reduction of intraocular pressure was--3.5 +/- 0.2,--4.3 +/- 0.2 and--4.6 +/- 0.3 mmHg at 2, 4, and 8 weeks, respectively (paired t test). In the currently-prescribed drug group, the reduction of intraocular pressure was--4.1 +/- 0.2,--4.4 +/- 0.3 and--4.6 +/- 0.2 mmHg at 2, 4, and 8 weeks(paired t test). The safety profile was similar in both groups, and the tolerance for the long-acting eye drops was as good as for the currently-prescribed eye drops. CONCLUSION: Because the efficacy of both drugs was equivalent, with an identical safety profile, the long-acting eye drops seem to be an efficacious formulation for clinical use in Japanese glaucoma patients.

Environmentally responsive ophthalmic gel formulation of carteolol hydrochloride.

Environmentally responsive gel formulation for ocular controlled delivery of carteolol hydrochloride (HCl) was developed in an attempt to improve ocular bioavailability and hence decrease its systemic absorption and side effects. The viscosity and the ability of the prepared formulations to deliver carteolol HCl in vitro and in vivo were monitored and compared with an aqueous commercial solution. The effect of polymer concentration and drug concentration on the in vitro release of carteolol HCl was examined. Gelrite formulations showed pseudoplastic behavior with thixotropic characteristics and the viscosity of the prepared systems increased as the concentration of the polymer increased. At fixed drug concentrations, as the Gelrite concentration increased, the drug release decreased. At fixed polymer concentrations, as the drug concentration increased the release of drug increased. Gelrite formulation (0.4% w/w) containing 1% drug showed significantly improved bioavailability compared with the commercial aqueous solution (Arteoptic 1%). The developed in situ gel formulation showed potential for use as delivery systems with superior ocular bioavailability of carteolol HCl.

Comparison of the additive effects of nipradilol and carteolol to latanoprost in open-angle glaucoma.

PURPOSE: To compare the effects of nipradilol and carteolol on intraocular pressure (IOP) when added to latanoprost treatment for glaucoma patients. METHODS: Fifty patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two groups randomly. One group received nipradilol 0.25% twice daily (nipradilol preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily (carteolol preceding group; n = 25), for 3 months in addition to latanoprost. Then, nipradilol and carteolol were switched, and the subjects were treated for 3 more months. One eye was selected randomly for analysis. RESULTS: In the nipradilol preceding group, IOP was 21.4 +/- 2.3 mmHg (mean +/- SD) at baseline, and 16.8 +/- 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of nipradilol decreased IOP to 15.8 +/- 1.7 mmHg, and the change to carteolol, to 15.3 +/- 2.0 mmHg. In the carteolol preceding group, IOP was 21.2 +/- 2.0 mmHg at baseline, and 17.0 +/- 2.1 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 +/- 1.8 mmHg, and the change to nipradilol, to 16.3 +/- 1.9 mmHg. Additional IOP reduction was greater with carteolol than with nipradilol (cross-over analysis of variance; P = 0.0005). CONCLUSIONS: Both nipradilol and carteolol have additive effects when used in combination with latanoprost. Carteolol, however, may have a more potent effect than nipradilol.

Randomized, Controlled, Phase 3 Trials of Carteolol/Latanoprost Fixed Combination in Primary Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: To assess the intraocular pressure (IOP)-lowering effects and safety of a carteolol/latanoprost fixed combination drug (OPC-1085EL) vs latanoprost (Study 1) and carteolol (Study 2) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). DESIGN: Multicenter, randomized, evaluator-masked (Study 1)/double-masked (Study 2), parallel-group studies. METHODS: Setting: Twenty-eight clinical sites (Study 1) and 19 clinical sites (Study 2) in Japan. STUDY POPULATION: Outpatients with bilateral POAG or OH whose predose IOP was 18 to <35 mm Hg in the study eye after 4 weeks' treatment with latanoprost (Study 1) or carteolol (Study 2) (defined as baseline). INTERVENTION: In Study 1, 237 patients applied OPC-1085EL (n = 118) or latanoprost (n = 119) for 8 weeks. In Study 2, 193 patients applied OPC-1085EL (n = 78), carteolol (n = 78), or carteolol/latanoprost concomitant therapy (n = 37) for 8 weeks. MAIN OUTCOME MEASURE: Adjusted mean IOP reduction at predose from baseline to week 8. RESULTS: In Study 1, the adjusted mean IOP reductions (95% confidence interval [CI]) were 2.9 (2.5-3.3) mm Hg and 1.6 (1.2-2.0) mm Hg in the OPC-1085EL and latanoprost groups, respectively (P < .0001). In Study 2, the adjusted mean IOP reductions (95% CI) were 3.5 (3.1-3.9) mm Hg and 1.6 (1.2-2.0) mm Hg in the OPC-1085EL and carteolol groups, respectively (P < .0001). All adverse drug reactions of OPC-1085EL observed in both studies were mild in severity and only 1 patient in each study discontinued because of an adverse drug reaction. CONCLUSIONS: OPC-1085EL is superior to latanoprost or carteolol alone in terms of lowering IOP, and was well tolerated.

Cough associated with the use of captopril.

Captopril is an orally active angiotensin-converting enzyme inhibitor that has been widely used in treating hypertension. We present a case of cough associated with captopril treatment in a patient with essential hypertension.

Effect of topical carteolol on the normal human retinal circulation.

The effect of topical carteolol 1%, a beta-adrenergic blocker with intrinsic sympathomimetic activity, on the retinal circulation was investigated in 15 normal subjects using laser Doppler velocimetry and monochromatic fundus photography. In a double-masked randomized design, one eye received one drop of carteolol 1% and the fellow eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were determined in a major temporal vein of each eye just before instillation of the drops and then 120 min later. No significant changes in heart rate or mean brachial artery blood pressure were detected after treatment. Intraocular pressure decreased by 28% in the carteolol-treated eye (P less than 0.0001) and by 15% in the placebo-treated eye (P less than 0.001). No significant changes in vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were observed in the carteolol-treated eyes (0.3%, 4.3%, and 3.6%, respectively) or the placebo-treated eyes (0.5%, 5.8%, and 6.7%, respectively).

Intracerebral penetration of carteolol hydrochloride in rats.

To elucidate the penetrability of carteolol, a beta-adrenoceptor antagonist (beta-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 microgram/g at 2 h postdosing and declined with a half-life of 3.7 h, and the Cmax and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059-0.091 microgram/g and 0.321-0.443 microgram/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6-0.8 h and 1.3-1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability.

Effects of topical adrenergic agents on tissue circulation in rabbit and human optic nerve head evaluated with laser speckle tissue circulation analyzer.

The effects of topical adrenergic agents on the tissue circulation of the optic nerve head (ONH) were studied in animal and human eyes with use of a laser speckle tissue circulation analyzer. Drugs studied were nipradilol, a beta1-2-blocker with weak alpha-blocking and nitroglycerinlike activities; bunazosin, a selective alpha1-blocker; carteolol, a beta1-2-blocker with intrinsic sympathomimetic activity; and betaxolol, a selective beta1-blocker. In the animal experiment, one eye each of nine albino rabbits received 0.25% nipradilol (N = 9) twice daily for 15 days or 0.01% bunazosin (N = 10) twice daily for 20 days; the fellow eye received the vehicle of each drug in a randomized masked design. Normalized blur (NB) in an area of ONH free of visible surface vessels, a quantitative index of peripheral blood velocity in ONH, was measured under general anesthesia before treatment and 2 hours after the last instillation on the 15th or 20th day. At 15 days, intraocular pressure and NB in the nipradilol-treated eyes decreased by 4.3 mm Hg (P < 0.01) and increased by 15.9% (P < 0.01), respectively, while those in the vehicle-treated eyes showed little change. At 20 days NB in both bunazosin- and vehicle-treated eyes showed little change, while intraocular pressure decreased only in the bunazosin-treated eyes (P < 0.01). In the human volunteer experiment NB was averaged over five pulses (mean NB) in both eyes before and 1.5, 3.0 and 4.5 hours after a 30 microL instillation of the vehicle of carteolol or betaxolol to serve as a control. Intraocular pressure, blood pressure and pulse rate were also measured. One week later a 30 microL drop of 2.0% carteolol (N = 6) or 0.5% betaxolol (N = 10) was instilled in one randomly chosen eye and the vehicle for each drug in the other eye, and those parameters were measured as above in a double-masked manner. In the carteolol experiment, mean NB in both eyes was significantly higher at 3 hours than it was in the control experiment (P < 0.05), while intraocular pressure was significantly lower in both eyes and blood pressure and pulse rate showed little change. In the betaxolol experiment, intraocular pressure at 1.5 hours and blood pressure at 4.5 hours were significantly lower than those in the control experiment (P < 0.05), while mean NB and pulse rate showed little change. In summary, using the laser speckle method we found that topical nipradilol and carteolol increase ONH blood velocity in rabbits and humans, respectively. This finding suggests that some topical beta-blockers used clinically may influence the ONH tissue circulation in patients and that this method may be used in clinical situations to assess the effect of various drugs on ONH circulation.

Topical ophthalmic beta-adrenergic blockade for the treatment of glaucoma and ocular hypertension.

Since the late 1970s, topical beta-adrenergic blockers have been the drugs of choice in treating ocular hypertension and associated glaucoma. The currently available drugs are timolol, betaxolol, levobunolol, metipranolol, and carteolol. All reduce intraocular pressure by decreasing the production of aqueous humor. Although these drugs are applied locally in the eye, they may enter the general circulation and reach concentrations high enough to cause systemic effects, including alterations in heart rate and rhythm, bronchoconstriction, dyslipidemia, and central nervous system abnormalities. Interactions with other drugs may also occur. Ocular beta- blockers differ in beta 1-selectivity (betaxolol is beta 1-selective, whereas the other drugs are nonselective) and in intrinsic sympathomimetic activity (ISA) or partial agonist properties (only carteolol possesses ISA). These differences give betaxolol and carteolol potential advantages in minimizing certain side effects. The advantage of betaxolol vis-à-vis systemic side effects is more clearly established than that of carteolol. Further systematic study is needed to determine what advantages, if any, are conferred by the presence of ISA.

Bronchial and cardiovascular effects of ocular topical B-antagonists in asthmatic subjects: comparison of timolol, carteolol, and metipranolol.

B antagonists eye drops are most effective for the treatment of chronic open angle glaucoma. By this way of administration they have a very good systemic bioavailability. Bronchial, and cardiovascular effects of three of these topicals: timolol, carteolol and metipranolol have been evaluated in three parallel groups of asthmatic patients. The three topics induce bronchoconstriction without significant difference between them, and lower heart rate (sometimes very intensely) whatever the B antagonist studied. From these data, it is recommended to practitioners to follow carefully the rules of administration of B blockers, even in eye drops.