Transscleral Coulomb-controlled iontophoresis of methyl prednisolone into the rabbit eye: Influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels
Transscleral Coulomb-controlled iontophoresis of methyl prednisolone into the rabbit eye: Influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels
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DOI：
10.1006/exer.2001.1098
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发表时间：
2002-01-01
影响因子：
3.4
通讯作者：
Parel, JM
中科院分区：
文献类型：
--
作者：
Behar-Cohen, FF;El Aouni, A;Parel, JM
与使用皮质类固醇治疗眼部疾病相关的主要问题是局部给药时其对眼后段的眼内渗透性差，以及全身给药时其继发性副作用。为了避免这些问题，正在开发更有效的当地交付方法和技术。本研究的目的是：（1）研究半琥珀酸甲基强的松龙（HMP）经巩膜库仑控制离子导入（CCI）系统眼内给药后或静脉注射（i. v.）在兔中注射，（2）测试CCI系统对于治疗的眼睛的安全性和（3）比较CCI递送与静脉内注射后HMP眼内分布的药代动力学曲线。对于评价的每个参数，使用6只兔眼。对于CCI系统，分析了两种[IMP]浓度（62.5和150 mg ml（-1））、不同电流强度和治疗持续时间。在作为对照的兔子中，将HMP输注到CCI装置中，但不施加电流。对于静脉给药，使用10 mg/kg HMP（62.5 mg/ml）溶液。临床观察家兔的眼毒性证据。在给药后的不同时间点，处死家兔，通过高压液相色谱法（HPLC）采集眼内液和组织中的甲基强的松龙（MP）浓度。在接受CCI的组中，所有眼组织和液体中的NIP浓度与所用电流的强度（0.4、1.0和2.0 mA/0.5 cm（2））及其持续时间（4和10 min）有关。持续和最高水平的MP实现在脉络膜和视网膜的最高电流和10分钟持续时间的CCl处理的兔眼。CCI后未观察到临床毒性或组织学病变。在未应用或电流的CCI对照组中，在眼组织中发现可忽略不计的MP量。与静脉给药相比，CCI达到了更高和更持久的组织浓度，全身吸收可忽略不计。这些数据表明，使用CCI，可以在兔眼的眼内组织和流体中安全地实现高水平的NIP。使用该系统，MP的眼内组织水平高于静脉注射后达到的水平。此外，如果需要，可以根据电流强度和治疗持续时间调节CCI达到的药物水平。因此，CCI可用作将高水平UP递送至前节和后节的眼内组织的替代方法。(C)2002年爱思唯尔科学有限公司
The major problems associated with the use of corticosteroids for the treatment of ocular diseases are their poor intraocular penetration to the posterior segment when administered locally and their secondary side effects when given systemically. To circumvent these problems more efficient methods and techniques of local delivery are being developed. The purposes of this study were: (1) to investigate the pharmacokinetics of intraocular penetration of hemisuccinate methyl prednisolone (HMP) after its delivery using the transscleral Coulomb controlled iontophoresis (CCI) system applied to the eye or after intravenous (i.v.) injection in the rabbit, (2) to test the safety of the CCI system for the treated eyes and (3) to compare the pharmacokinetic profiles of HMP intraocular distribution after CCI delivery to i.v. injection. For each parameter evaluated, six rabbit eyes were used. For the CCI system, two concentrations of [IMP (62.5 and 150 mg ml(-1)), various intensities of current and duration of treatment were analyzed. in rabbits serving as controls the HMP was infused in the CCI device but without applied electric current. For the i.v. delivery, HMP at 10 mg, kg(-1) as a 62.5 mg ml-1 solution was used, The rabbits were observed clinically for evidence of ocular toxicity. At various time points after the administration of drug, rabbits were killed and intraocular fluids and tissues were sampled for methylprednisolone (MP) concentrations by high pressure liquid chromatography (HPLC). Histology examinations were performed on six eyes of each group.Among groups that received CCI, the concentrations of NIP increased in all ocular tissues and fluids in relation to the intensities of current used (0.4, 1.0 and 2.0 mA/0.5 cm(2)) and its duration (4 and 10 min). Sustained and highest levels of MP were achieved in the choroid and the retina of rabbit eyes treated with the highest current and 10 min duration of CCl. No clinical toxicity or histological lesions were observed following CCI. Negligible amounts of MP were found in ocular tissues in the CCI control group without application or current. Compared to i.v, administration, CCI achieved higher and more sustained tissue concentrations with negligible systemic absorption. These data demonstrate that high levels of NIP can be safely achieved in intraocular tissues and fluids of the rabbit eye, using CCI. With this system, intraocular tissues levels of MP are higher than those achieved after i.v. injection. Furthermore, if needed, the drug levels achieved with CCI can be modulated as a function of current intensity and duration of treatment. CCI could therefore be used as an alternative method for the delivery of high levels of UP to the intraocular tissues of both the anterior and posterior segments. (C) 2002 Elsevier Science Ltd.