Intracerebral penetration of carteolol hydrochloride in rats

To elucidate the penetrability of carteolol, a β-adrenoceptor antagonist (β-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 μg/g at 2 h postdosing and declined with a half-life of 3.7 h, and the C_max 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 μg/g and 0.321–0.443 μg/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. Received: 30 October 1996/Final version: 16 December 1996     

他氟前列素滴眼液联合盐酸卡替洛尔滴眼液治疗开角型青光眼的疗效观察

目的探究他氟前列素滴眼液联合盐酸卡替洛尔滴眼液治疗开角型青光眼的临床疗效。方法选取2016年4月—2017年4月于宝鸡市人民医院治疗的80例(146眼)高眼压型原发性开角型青光眼患者为研究对象,根据数字表法将患者分为对照组(40例72眼)和治疗组(40例74眼)。对照组给予盐酸卡替洛尔滴眼液,1滴/次,2次/d。治疗组在对照组基础上给予他氟前列素滴眼液,1滴/次,1次/d。4周为1个疗程,两组均治疗3个疗程。观察两组患者的临床疗效,比较治疗前后两组患者的视盘参数、杯盘直径比、角膜中央厚度、前房深度和眼压。结果治疗后,对照组和治疗组的改善率分别为80.56%、97.30%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者盘沿面积(RA)、盘沿容积(RV)和视盘容积(DV)指数均显著升高,同组治疗前后比较差异具有统计学意义(P0.05)。治疗后,治疗组的视盘参数显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者水平杯盘直径比(C/D)显著升高,垂直C/D显著降低,同组治疗前后比较差异具有统计学意义(P0.05)。治疗后,治疗组的杯盘直径比改善程度显著优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组角膜中央厚度均显著降低,同组治疗前后比较差异具有统计学意义(P0.05)。治疗后,治疗组的角膜中央厚度显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者眼压均显著降低,同组治疗前后比较差异具有统计学意义(P0.05)。治疗后,治疗组眼压显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论他氟前列素滴眼液联合盐酸卡替洛尔滴眼液治疗开角型青光眼患者具有较好的临床疗效,可有效提高患者视力,改善视盘参数和视网膜神经纤维层厚度,具有一定的临床推广应用价值。     

β受体阻滞剂治疗婴儿血管瘤中国专家共识

【摘要】 β受体阻滞剂是目前治疗婴儿血管瘤的一线药物,主要包括口服普萘洛尔和外用噻吗洛尔/卡替洛尔滴眼液。β受体阻滞剂药物选择及给药方式主要根据患儿年龄、瘤体部位、分型、分类及大小等因素综合决定。本共识对口服普萘洛尔的适应证及禁忌证、治疗起始时间及剂量、疗程与停药指征、用药期间注意事项和不良反应的监测及处理和特殊人群治疗剂量、疗程以及外用β受体阻滞剂适应证、应用具体方法等进行总结,希望为皮肤科及相关专业医生规范应用β受体阻滞剂治疗婴儿血管瘤提供参考依据。     

The attenuating effect of carteolol hydrochloride, a β-adrenoceptor antagonist, on neuroleptic-induced catalepsy in rats

It is known that β-adrenoceptor antagonists are effective in the treatment of akathisia, one of the extrapyramidal side effects that occur during neuroleptic treatment. Neuroleptic-induced catalepsy, a model of neuroleptic-induced extrapyramidal side effects, was considered suitable as a model for predicting neuroleptic-induced akathisia in humans, although neuroleptic-induced catalepsy was not considered a specific test for neuroleptic-induced akathisia. Therefore, the effects of carteolol, a β-adrenoceptor antagonist, on haloperidol-induced catalepsy in rats were behaviorally studied and compared with those of propranolol and biperiden, a muscarinic receptor antagonist. Carteolol, as well as propranolol and biperiden, inhibited the haloperidol-induced catalepsy. The inhibitory effect of carteolol was almost comparable to that of propranolol, but was weaker than that of biperiden. Carteolol did not evoke postsynaptic dopamine receptor-stimulating behavioral signs such as stereotypy and hyperlocomotion in rats. Carteolol did not antagonize the inhibitory effects of haloperidol on apomorphine-induced stereotypy and locomotor activity in rats. In addition, carteolol did not evoke 5-HT_1A receptor-stimulating behavioral signs such as flat body posture and forepaw treading and did not inhibit 5-hydroxytryptophan-induced head twitch in rats. Finally, carteolol did not inhibit physostigmine-induced lethality in rats. These results strongly suggest that carteolol improves haloperidol-induced catalepsy via its β-adrenoceptor antagonistic activity and is expected to be effective in the treatment of akathisia without attenuating neuroleptic-induced antipsychotic effects due to its postsynaptic dopamine receptor antagonistic activity. Received: 7 March 1996/ Final version: 27 November 1996     

Effects of carteolol on the electroretinogram in the perfused cat eye

Carteolol, a nonselective beta-antagonist, was administered intra-arterially in perfused cat eyes. Carteolol increased both photopic and scotopic electroretinogram b-wave amplitude dose-dependently and reversibly, but carteolol failed to induce significant changes in the flow rate of perfusate. This study suggests that carteolol may increase selectively the retinal perfusion flow rate, though it did not reflect the total perfusion flow, or carteolol may have an interaction with retinal beta-adrenergic receptors related to the origin of the b-wave. These ideas are supported by carteolol's intrinsic sympathomimetic activity and effects on endothelium of vessels.     

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.     

山莨菪碱联合盐酸卡替洛尔滴眼液在延缓近视发展中的作用

目的:探讨0.5%消旋山莨菪碱滴眼液和2%盐酸卡替洛尔滴眼液治疗儿童近视的有效性。方法:患者双眼点用0.5%消旋山莨菪碱滴眼液和2%盐酸卡替洛尔滴眼液,早晚各一次。对用药前后的年近视发展度、眼轴、眼压和视力进行配对t检验,采用用药前后自身对照。定期观察近视发展情况。结果:年龄7～14岁(平均10.12±2.56岁),接受治疗时间1.0～2.5年。用药前后年近视发展度分别为(-1.05±0.53)D/年和(-0.56±0.55)D/年。用药后年近视发展度明显少于用药前(P<0.01)。用药前及用药后随诊矫正视力分别为4.83±0.12和4.94±0.23,用药后末次随诊矫正视力优于用药前(P<0.01)用药前后眼轴分别为(23.84±1.66)mm和(24.50±1.89)mm,用药后眼轴较用药前增长(P>0.05)。结论:点用山莨菪碱联合盐酸卡替洛尔滴眼液具有延缓近视发展的作用。     

Comparison of carteolol plasmatic levels after repeated instillations of long-acting and regular formulations of carteolol 2% in glaucoma patients

Background A new long-acting (LA) formulation of carteolol 2% instilled once daily has been shown to provide a therapeutic effect similar to that of the regular formulation of carteolol 2% instilled twice daily. This study was designed to test whether the new formulation reduces the systemic delivery of carteolol. Methods In this double-masked, randomised, intra-subject comparative study, 23 patients with bilateral primary open-angle glaucoma or bilateral ocular hypertension received sequentially, according to the randomised order of administration, each of the 2 following treatments: carteolol 2% LA once daily for 2 months and carteolol 2% regular twice daily for 2 months. Treatments were instilled in both eyes throughout the study period. At the end of each period of treatment, blood samples were taken immediately before the last morning instillation (residual time), then 30 min, 1 h, 2 h and 4 h after this instillation in order to measure the carteolol plasma concentrations. Results The mean values of maximal plasma concentration (C_max), residual level and area under the curve obtained following carteolol 2% LA treatment were significantly lower than the values obtained after carteolol 2% regular treatment (mean±SD): C_max (ng/ml): 1.72±0.85 versus 3.64±3.65; residual level (ng/ml): 0.70±0.58 versus 1.80±0.84; area under the curve (ng/ml×h): 5.50±2.66 versus 10.27±5.46. Regarding safety, two drug-related, non-serious adverse events were reported in the LA group: one case of moderate, superficial, punctate keratitis and one case of “bitter taste in the throat.” Both treatments appeared to be well tolerated. Conclusions The data from this study showed that the systemic delivery of carteolol is lower for the once-daily LA formulation than for the regular twice-daily formulation. Consequently, long-acting carteolol eye-drops should reduce the risk of β-blocking systemic side effects. This study has been sponsored by Bausch & Lomb. P. Renard, J.L Kovalski, I. Cochereau, S. Jaulerry, W. Williamson and P.P. Elena have no proprietary interest with Bausch & Lomb. M. Lablache-Combier, C. Allaire and R. Siou-Mermet are employees of Bausch & Lomb. This work was partly presented at the ARVO Congress, Fort Lauderdale, USA, 25–29 April 2004.     

噻吗洛尔与卡替洛尔治疗原发性开角型青光眼的效果及安全性分析

目的观察噻吗洛尔与卡替洛尔治疗原发性开角型青光眼的临床效果及安全性。方法选取2010年8月至2011年7月成都市龙泉驿区第一人民医院眼科收治的原发性开角型青光眼患者90例,依据用药方案不同分为三组:每组30例,A组采用噻吗洛尔治疗、B组采用卡替洛尔治疗,C组采用噻吗洛尔联合卡替洛尔治疗,比较三组患者的临床疗效及不良反应。结果三组患者经过6个月治疗后,其眼压较治疗前均有显著下降(P<0.05),但C组患者眼压下降的程度显著高于A、B两组(P<0.05);C组患者眼压达目标值率显著高于A组和B组(P<0.05);C组患者的达标平均时间显著低于A组和B组(P<0.05)。结论噻吗洛尔和卡替洛尔在一定的治疗时间内均能有效控制原发性青光眼患者的眼压,但两者联用在改善患者眼压的效率方面较单用有明显优势,且药物不良反应并未因为联合用药而增加。     

Effects of the non-selective beta-adrenoceptor blocking agent, carteolol, on platelet function, blood coagulation and viscosity

We have studied the effect of a new beta-adrenergic blocker, carteolol, on platelet function, blood coagulation and viscosity in 10 healthy male volunteers. Following carteolol (5 mg orally) we were able to demonstrate significant inhibition of platelet aggregation to ADP (p less than 0.05) and adrenaline (p less than 0.01) after 5 hours, but not at 2 or 24 hours. This maximum inhibition of platelet aggregation corresponded to peak plasma concentrations of carteolol measured. The platelet release reaction, as measured by plasma levels of the platelet specific protein beta-thromboglobulin (BTG) was unaltered and there was no significant effect on a panel of coagulation tests or on blood viscosity.