阿昔洛韦原位胶化滴眼液的眼内药物动力学研究

目的：考察阿昔洛韦原位胶化滴眼液滴入眼睛后在眼房水中的药物代谢动力学，并与市售阿昔洛韦滴眼液进行比较。方法：两种制剂滴眼后，采用反相高效液相色谱法测定不同时间点的兔眼房水中阿昔洛韦的浓度。结果：原位胶化滴眼液和市售滴眼液滴眼后，除0.25h时间点外，其余各时间点阿昔洛韦原位胶化滴眼液治疗组的房水药物浓度较市售阿昔洛韦滴眼液治疗组明显增高（P＜0．05）。原位胶化滴眼液的生物利用度是滴眼液的2．67倍。用胶化滴眼液后6.5h，房水中仍可测出阿昔洛韦的浓度，而用滴眼液后5.5h，房水中已测不出阿昔洛韦的浓度。结论：阿昔洛韦原位胶化滴眼液能提高药物的生物利用度，增强疗效，并减少给药频率。     

雷帕霉素纳米粒滴眼液兔眼部药物分布研究

目的:比较雷帕霉素纳米粒滴眼液及其一般滴眼液滴眼后,在兔眼房水及角膜组织中药物分布。方法:将健康无眼疾新西兰白兔随机分为试验组与对照组,分别每眼结膜囊内单次给雷帕霉素纳米粒滴眼液及其一般滴眼液50μL。于滴眼后15、30、60、360和720min取材,采用高效液相色谱法(HPLC)测定兔眼不同时间房水及角膜组织中雷帕霉素浓度。结果:在用药后15～720min内实验组各时间点房水和角膜组织中的药物浓度均明显高于对照组。实验组内30～720min各时间点房水和角膜组织中的药物浓度比较无统计学差异。结论:雷帕霉素纳米粒滴眼液同一般滴眼液相比明显延长药物在眼部的停留时间,增加房水和角膜组织中的药物浓度,且能够维持组织中药物浓度的平稳。     

乳酸左氧氟沙星滴眼液在兔眼房水中的药代动力学

目的 :测定乳酸左氧氟沙星 (LVFX)滴眼液单次滴眼后不同时间兔眼房水的药物浓度 ,计算其药动学参数。方法 :取32只大白兔分为8组 ,各组于用药后0 125、0 25、0 50、0 75、1 0、2 0、3 0、4 0h取眼房水 ,用高效液相色谱法测定药物浓度。结果 :用3p87药动学程序拟合符合一室开放模型 ,药物在房水中Tmax0 940h、Cmax 0 592μg/ml、T1/2(Ka)0 479h、T1/2(Ke)0 919h。结论 :单次滴眼后兔房水中LVFX峰浓度均高于大多数致病菌的MIC90,LVFX滴眼液可用于眼内感染的临床治疗和预防。     

玻璃酸钠在氯霉素滴眼液中的作用

目的研究玻璃酸钠(SH)在氯霉素滴眼液中所起的作用。方法采用对比实验法,测定氯霉素滴眼液和含SH的氯霉素滴眼液的运动黏度。给家兔的2只眼结膜囊内分别滴入氯霉素滴眼液和含SH的氯霉素滴眼液各50μL,采集泪液测定药物浓度,对2种滴眼液做家兔眼刺激实验。结果含SH的氯霉素滴眼液比氯霉素滴眼液的运动黏度大,对眼部不引起刺激性,可以延长药物在泪液中的滞留时间。结论SH能增加氯霉素滴眼液的黏度,延长药物在泪液中的滞留时间,提高药物疗效。     

利奈唑胺滴眼液在家兔房水中的浓度及其药代动力学特征

目的 探讨利奈唑胺滴眼液单次滴兔眼后在房水中的浓度及其药代动力学特征.方法 54只新西兰家兔,局部滴人利奈唑胺滴眼液50ml,采用高效液相色谱法测定兔眼房水中利奈唑胺的药物浓度,计算其药代动力学参数.结果 给药后0～120h,利奈唑胺在兔眼房水中的达峰浓度为(84.92±67.04)μg/ml,消除半衰期t1/2为(4...     

不同眼用剂型中秦皮苷的兔泪液药物动力学

目的：为了解滴眼液、速释眼膜和缓释眼膜中秦皮苷在兔泪液中的药物动力学差别。方法：采用薄层扫描法测定了不同时间兔泪液中秦皮苷的浓度。药物浓度时间数据采用非隔室统计矩原理进行分析。结果：滴眼液、速释眼膜、缓释眼膜中秦皮苷的泪液药物动力学参数间差异具非常显著性（Ｐ＜０．０１）,ＭＲＴ分别为１４．４,２６．０,８８．５ｍｉｎ,速释眼膜和缓释眼膜的ＡＵＣ与剂量的比值分别为滴眼液比值的１．６６和２．５５。结论：缓释眼膜较优,在泪液中维持较长时间的药物浓度,可以提高药物疗效。     

N-三甲基壳聚糖包衣维生素A阳离子脂质体原位凝胶的兔房水药动学研究

目的:比较N-三甲基壳聚糖(TMC60)包衣的维生素A棕榈酸酯(VAP)阳离子脂质体-原位凝胶(TMC60-VAPL-ISG组)与市售VAP凝胶(诺沛组)在兔眼房水的药物动力学.方法:采用自身对照,两种制剂滴用后,用HPLC法测定不同时间点的兔眼房水中的VAP浓度,用3P97软件拟合求得药动学参数.结果:用药0.25 h后,TMC60-VAPL-ISG组各时间点房水内药物浓度均明显高于诺沛组,房水药物浓度-时间曲线下面积(AUC0-24)也明显高于诺沛组(P<0.05).结论:TMC60-VAPL-ISG可明显延长药物在眼部的滞留时间,增加房水中药物浓度,显著提高VAP的眼部生物利用度.     

阿昔洛韦眼用凝胶在兔离体角膜中的渗透释药行为研究

目的:研究阿昔洛韦眼用凝胶在兔离体角膜中的渗透释药行为。方法:以谷胱甘肽缓冲液作为释放介质,采用高效液相色谱法测定阿昔洛韦眼用凝胶及阿昔洛韦滴眼液在兔离体角膜中的累积渗透释药量,并绘制曲线。结果:阿昔洛韦眼用凝胶的渗透释药曲线符合一级释药方程;0·25h时阿昔洛韦滴眼液的累积渗透释药量高于阿昔洛韦眼用凝胶,0·25h以后则相反。结论:在给药后很短时间内(0·25h),阿昔洛韦滴眼液的房水药物浓度要高于阿昔洛韦眼用凝胶,但凝胶在眼部滞留时间较长,且角膜有一定的药物储库作用。     

加替沙星原位凝胶的体外释放及兔眼房水药动学研究

目的:研究加替沙星温敏型凝胶及离子敏感型凝胶的体外释药特性、机制及在家兔房水中的药动学特征。方法:采用无膜溶出法考察凝胶的体外溶蚀及药物释放;局部滴入加替沙星凝胶剂或滴眼液,以HPLC法测定兔眼房水中的药物浓度,计算药动学参数。结果:凝胶溶蚀与药物释放速率均随着振荡频率和释放面积的增加而增大,两者具有明显的相关性;给药后8 h内,温敏、离子敏感凝胶组与滴眼液组房水中药物峰浓度分别为(1.38±0.11)μg·mL-1、(1.19±0.20)μg·mL-1及(0.50±0.06)μg·mL-1,达峰时间分别为2.0 h、1.0 h和1.0 h,AUC0-8h分别为(5.61±0.25)μg·h·mL-1、(4.50±0.19)μg·h·mL-1和(1.29±0.22)μg·h·mL-1。结论:凝胶溶蚀与药物释放行为符合零级动力学方程,药物的释放主要由凝胶溶蚀决定。加替沙星凝胶剂较滴眼液可显著提高房水中的药物浓度及生物利用度并延长了作用时间。     

2种更昔洛韦滴眼液在家兔眼部的生物等效性比较

目的:比较更昔洛韦壳聚糖滴眼液与不含壳聚糖的相同处方更昔洛韦滴眼液的眼部药动学与相对生物利用度。方法:取日本大耳兔分为实验组(更昔洛韦壳聚糖滴眼液)与对照组(更昔洛韦滴眼液),双侧眼分别滴入相应的更昔洛韦滴眼液50μL,分别于不同时间取泪液、角膜、房水,采用高效液相色谱法测定药物浓度并计算药动学参数。结果:实验组与对照组给药后泪液药物t1/2分别为15.41、16.22min,角膜t1/2分别为45.21、32.55min,房水t1/2为59.43、48.53min,房水Cmax分别为2.03、1.22μg·mL-1,实验组泪液、角膜与房水中药物AUC0→240分别是对照组的1.66、1.89、2.77倍。结论:与不含壳聚糖滴眼液比较,更昔洛韦壳聚糖滴眼液生物利用度显著提高。     

复方两性霉素B眼用凝胶在兔眼的药代动力学

目的 观察兔眼局部应用复方两性霉素B眼用凝胶的眼内通透性和药代动力学特征.方法 将30只新西兰大白兔分为10组,每组3只（6只眼）,分别于30只兔双眼点复方两性霉素B眼用凝胶50μl后,5、15、30、45、60、90、120、180、240和360 min时取泪液,并迅速处死后取角膜和房水,测定两性霉素B和利福平的含量,计算药代动力学参数.结果 利福平有良好的眼内通透性,但房水中检测不到两性霉素B;两性霉素B和利福平在兔角膜中的达峰时间为20.96和7.57 min、达峰浓度为3.32和25.37μg/g、消除半衰期为45.34和31.69 min、浓度-时间曲线下面积为299.44和1368.91（min·mg）/g.结论 复方两性霉素B眼用凝胶可用于治疗外眼真菌感染性疾病,但其能否用于内眼真菌感染,仍需进一步研究.     

西罗莫司滴眼液在兔眼房水内的药动学

目的探讨西罗莫司滴眼液单次滴兔眼后在房水中的药动学特征。方法 40只新西兰大白兔,局部滴入西罗莫司滴眼液50μL,采用高效液相色谱法测定兔眼房水中西罗莫司的药物浓度,用DAS1.0软件计算药动学参数。结果给药后0～120 h,西罗莫司在兔眼房水中的ρ_(max)为(84.92±37.04)μg·mL~(-1)(-1),t_(1/2)为(43.28±18.11)h,AUC_(0-6)为(1 747.44±571.36)μg·h·mL~(-1),AUC_(0-∞)为(2 335.25±702.42)μg·h·mL~(-1)。空白房水不干扰西罗莫司的含量测定。结论单次滴眼后西罗莫司可以快速穿透眼组织到达前房,并在房水中达到较高的药物浓度。     

兔角膜碱烧伤后角膜、房水和晶状体中NO与MDA含量的实验探讨

目的:探讨碱烧伤后角膜、房水、晶状体组织中一氧化氮(NO)与丙二醛(MDA)含量改变及其意义.方法:选择健康新西兰大白兔20只(40眼),经麻醉后,用直径9mm圆形滤纸浸透2mmol/L氢氧化钠,贴附于兔右眼角膜中央区,制作碱烧伤模型.72h后处死,取角膜、房水、晶状体,角膜及晶状体做组织匀浆,用比色法测量其NO和MDA的含量,左眼为正常对照组.结果:碱烧伤72h后角膜、房水、晶状体中NO和MDA含量较对照组显著升高(P＜0.01), MDA及NO各组中的含量经过方差分析均不相同,对角膜、房水、晶状体中MDA及NO进行相关性分析,两者为正相关关系.结论:NO、MDA均参与了碱烧伤后眼部损伤的病理生理过程.     

加替沙星滴眼液在兔眼房水中的药动学

目的探讨加替沙星滴眼液单次滴兔眼后在房水中的药动学特征。方法24只新西兰家兔,局部滴入加替沙星滴眼液50μL,以高效液相色谱法测定兔眼房水中加替沙星的药物浓度,用DAS1.0软件计算药动学参数。结果给药后0.5～6 h,加替沙星在兔眼房水中的c_(max)为(0.31±s 0.06)mg·L~(-1),消除半衰期为(3.4±0.7)h,AUC_(0～6h)为(0.70±0.22)mg·h·L~(-1),AUC_(0～∞)为(0.7±0.3)mg·h·L~(-1)。空白房水不干扰加替沙星的含量测定。结论加替沙星滴眼液单次滴兔眼后在眼房水中具有良好的药动学特征和组织通诱性。     

Determination of permeability coefficients of ophthalmic drugs through different layers of porcine, rabbit and bovine eyes

To treat ophthalmic diseases like glaucoma or inflammatory disorders topically applied ophthalmic formulations such as eye drops are usually used. In addition, novel ophthalmic implants releasing drug substances locally into different parts of the eye are available today. In the work presented here, the permeability coefficients of selected drugs (ciprofloxacin hydrochloride, lidocaine hydrochloride, timolol maleate) for ophthalmic tissues were determined using side-by-side diffusion chambers (so-called Ussing chambers). Sclera, conjunctiva, cornea, choroidea-retina-complex and a complex of conjunctiva-sclera-choroidea-retina were excised from fresh porcine, rabbit and bovine eyes. In the porcine eye tissues the highest P(app) values were obtained for conjunctiva with the exception of lidocaine. Therefore, it can be estimated that a certain amount of drug diffuses or is transported through conjunctiva after application. The P(app) values for sclera were also higher than those for cornea and even more, the surface area of sclera which is available for drug absorption is much larger than that of cornea when applying an implant. The obtained permeability coefficients for sclera and conjunctiva indicate that the administration of periocular implants can be an alternative to topically applied formulations. The complexes of the tissues were a significantly (p<0.01) stronger barrier to the investigated substances than the separated tissues. Distinct differences in permeability coefficients between the investigated animal tissues were observed. Overall the highest P(app) values for all mounted tissues were obtained with the rabbit, followed by porcine and bovine eyes. Because of these distinct interspecies differences one must be very careful when selecting the proper animal model for the permeability experiments.     

Penetration of topical and oral ofloxacin into the aqueous and vitreous humor of inflamed rabbit eyes

PURPOSE: This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits. METHODS: A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes were maintained as controls. The animals were divided randomly into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group, two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the protocol of the first group was applied. Aqueous and vitreous humor samples were taken 30 min after the last drop. Ofloxacin concentrations were measured by using HPLC. RESULTS: Mean aqueous levels of ofloxacin in control eyes were: 3.25 +/- 2.55 microg/ml in topical group. 4.58 +/- 5.39 microg/ml in topical-oral group. Mean aqueous levels in inflamed eyes were: 5.21 +/- 4.55 microg/ml in topical group, 10.34 +/- 8.88 microg/ml in topical-oral group. Mean vitreous levels of ofloxacin in control eyes were: 0.17 +/- 0.07 microg/ml in topical group, 1.30 +/- 1.23 microg/ml in topical-oral group. Mean vitreous levels in inflamed eyes were: 0.35 +/- 0.22 microg/ml in topical group, 3.48 +/- 2.69 microg/ml in topical-oral group. There was no significant difference among the groups (P > 0.05), however. CONCLUSIONS: The result of this study suggests that oral supplementation of ofloxacin to topical instillation increased the ocular levels of ofloxacin in the post-traumatic endophthalmitis model. Mean drug concentrations in aqueous and vitreous humors were above the 90% minimum inhibitory concentrations (MIC90) for most of the common microorganisms causing endophthalmitis in all eyes, except in the vitreous humors of the intact eyes instilled topically.     

Pharmacokinetics and efficacy of a ketorolac-loaded ocular coil in New Zealand white rabbits

Eye drops are considered standard practice for the delivery of ocular drugs. However, low patient compliance and low drug levels compromise its effectiveness. Our group developed a ketorolac-loaded ocular coil for sustained drug delivery up to 28 days. The aim of this study was to gain insight into the pharmacokinetics and efficacy of the ocular coil. The pharmacokinetics of the ketorolac-loaded ocular coil versus eye drops were tested in New Zealand White rabbits by repetitive sampling for 28 days. Efficacy of the ocular coil was also tested in New Zealand White rabbits. Ocular inflammation was induced where after the ocular coil was inserted, or eye drops, or no treatment was provided. The total protein concentration and cytokine levels were measured in tears, aqueous humor, and plasma at 4 h, 8 h, 24 h, 4 d, 7 d, 14 d, 21 d, and 28 d. Four h after inserting the ocular coil in the eye, ketorolac levels in aqueous humor and plasma were higher in the ocular coil group than in the eye drop group. Ketorolac released from the ocular coil could be detected up to 28 d in tears, up to 4 d in aqueous humor and up to 24 h in plasma. After inducing inflammation, both the ocular coil and eye drops were able to suppress prostaglandin E₂, TNFα and IL-6 levels in aqueous humor and plasma as compared to the group that received no treatment. To conclude, the ocular coil facilitated a sustained release of the drug and showed similar therapeutic benefit in suppressing post-operative inflammation as eye drops.     

盐酸小檗碱眼用温敏原位凝胶制备及兔眼房水内药动学特征

目的:制备盐酸小檗碱眼用温敏凝胶并考察其在家兔眼房水内的药动学特征。方法:以泊洛沙姆为温敏材料,盐酸小檗碱为模型药物制备眼用温敏原位凝胶,高效液相色谱法测定给药后不同时间兔眼房水中的盐酸小檗碱浓度,绘制药-时曲线,计算相关药动学参数。结果:盐酸小檗碱眼用温敏原位凝胶在兔眼内的吸收和消除过程呈线性二室模型动力学特征,其t1/2β、t1/2α,MRT、Tmax、Cmax、AUC0-τ和AUC0-∞分别为4.585 h,0.911 h,1.966 h,1 h,1.4 mg.L-1,2.561 mg.h.L-1,2.581 mg.h.L-1。结论:此方法可用于测定房水中盐酸小檗碱的浓度,对于盐酸小檗碱眼部局部给药药动学研究提供评价方法。