Intraocular levels of cefamandole compared with cefazolin after subconjunctival injection in rabbits.

We compared the intraocular pharmacokinetics of cefazolin with those of cefamandole, a recently marketed cephalosporin with enhanced activity against gram-negative bacilli. Following subconjunctival injection of 12.5 mg into infected eyes (S. aureus endophthalmitis) of pigmented rabbits, both drugs reached peak concentrations greater than 100 microgram/gm in cornea, sclera, and choroid-retina. The half-life was markedly shorter in sclera and choroid-retina than in cornea. Levels in the aqueous humor rose and fell more slowly than those in ocular tissues, reaching a maximum of only 5 to 10 microgram/ml. The pharmacokinetics of the two drugs were virtually identical in most intraocular sites. When cefazolin, which was less irritating than cefamandole by the subconjunctival route, was given in a dosage of 100 mg, levels in ocular tissues were increased by twofold to fourfold and in aqueous humor by 15-fold, compared to the concentrations produced by the 12.5 mg dosage. Levels in the vitreous humor were exceedingly low with both drugs; mean peak concentrations were 0.24 microgram/ml after the 12.5 mg dosage of cefamandole and less than 1.6 microgram/ml after the 100 mg dose of cefazolin.     

Intraocular penetration of gentamicin after subconjunctibal and retrobulbar injection .

We compared the ocular penetration of labeled with radioactive carbon gentamicin in squirrel monkeys after subconjunctival and retrobulbar administration. In both normal and infected (Staphylococcus aureus endophthalmitis) eyes, high concentrations of drug were achieved in the sclera and choroid-retina by both routes, while corneal levels were markedly higher after subconjunctival injection than after retrobulbar injection. Regional variations in concentration were evident in these tissues; the highest levels were clustered about the site of injection. Aqueous humor concentrations were lowest in the group with normal eyes treated by the retrobulbar route; vitreous humor levels were extremely low in normal eyes injected subconjunctivally. These data differ from those in rabbits, especially with regard to penetration of the vitreous humor of normal eyes. Interspecies differences were less marked in inflamed eyes. The two species were similar in demonstrating maximum access to the cornea and aqueous humor with subconjunctival injection, and equivalence of the two routes in penetrating the vitreous humor of the inflamed eyes.     

Ocular pharmacokinetics of subconjunctivally administered cyclosporine in the rabbit

The authors assessed the ocular toxicity and pharmacokinetics of subconjunctivally and intravenously administered cyclosporine in New Zealand white rabbits. Fifteen rabbits received a subconjunctival injection of 5 (five animals), 10 (five animals) or 25 (five animals) mg of cyclosporine in 0.1 mL (intravenous solution of Sandimmune [50 mg/mL]); 5 mg was found to be the maximum tolerable dose. This dose was given as a bolus to 36 other rabbits either subconjunctivally (18 animals) or intravenously (18 animals). In both groups the cyclosporine concentrations in the ocular compartments, blood and urine were measured by means of high-pressure liquid chromatography at 0.5, 1, 2, 4, 8 and 12 hours, three animals being assessed at each interval. Subconjunctival administration resulted in peak cyclosporine concentrations of 718 ng/mL in the aqueous humour and 1078 ng/mL in the vitreous humour, compared with no detectable levels in the aqueous humour and a peak concentration of 292 ng/mL in the vitreous following intravenous administration. The peak blood cyclosporine levels were 10 times lower after subconjunctival injection than after intravenous injection. The results indicate that subconjunctival administration is superior to intravenous administration in enhancing the ocular absorption of cyclosporine while minimizing systemic exposure in the rabbit.     

Regional ocular gentamicin levels after transcorneal and transscleral iontophoresis

Transcorneal and transscleral iontophoresis were compared to subconjunctival injection (control) in the delivery of gentamicin into rabbit eyes. Gentamicin levels in the corena, aqueous, and vitreous were measured by a fluorescence polarization assay at various time intervals after treatment. A mean peak corneal concentration of 376.1 micrograms/ml was achieved 2 hr after transcorneal iontophoresis. This was significantly higher than the level obtained in control eyes (P = 0.016). A mean peak aqueous humor concentration of 54.8 micrograms/ml occurred 2 hr after transcorneal iontophoresis. This was significantly higher than the peak level of 14.2 micrograms/ml after subconjunctival injection (P = 0.003). Inhibitory levels (approximately 5 micrograms/ml) were maintained in both aqueous and cornea for 8 hr after transcorneal iontophoresis. After transscleral iontophoresis, the mean peak vitreous humor concentration was 53.4 micrograms/ml at 16 hr and remained inhibitory through 24 hr; the peak aqueous level was 23.2 micrograms/ml and remained inhibitory for 24 hr. Peak drug concentrations in the vitreous were significantly higher than control (P = 0.026). Therapeutic vitreous humor levels were not achievable after transcorneal iontophoresis or subconjunctival injection. Potential corneal toxicity of transcorneal iontophoresis was demonstrated by measuring corneal thickness and endothelial cell counts prior to and 3 days after transcorneal iontophoresis of gentamicin and balanced saline solution (BSS) (control). No significant differences existed between eyes treated with gentamicin compared to those treated with BSS or when pre- versus postiontophoresis of gentamicin in the same eyes were compared. Transcorneal and transscleral iontophoresis may be an effective noninvasive method of delivering inhibitory levels of gentamicin to the cornea, aqueous humor, and vitreous for the treatment of intraocular infections.     

Hydrolysis of prednisolone succinate by esterase in rabbit ocular tissue

Prednisolone concentrations in serum after both subconjunctival and intravenous injections of prednisolone sodium succinate at a 1 mg/kg equivalent dose of prednisolone in rabbits were analyzed by regularly phased high-performance liquid chromatography. The systemic availability after subconjunctival injection was determined to be almost 1.0 by comparing areas under the serum concentration-time curves for both administration routes. The initial hydrolytic rate of prednisolone succinate ester was dependent on the amount of total protein in ocular tissue homogenates and fluids as well as that in serum. The rate followed Michaelis-Menten kinetics, with an almost consistent Michaelis constant. Although the maximum hydrolytic rate per unit amount of tissue protein was the highest in conjunctival tissue, followed by corneal tissue and serum, the esterase activity corrected by total protein in the whole rabbit body should be the highest in serum, followed by conjunctival tissue. These results indicate that prednisolone sodium succinate administered subconjunctivally is hydrolyzed rapidly by esterase and absorbed almost completely into the systemic circulation.     

Penetration and decay of meropenem into the human aqueous humor and vitreous.

The aim of this study was to determine the penetration of intravenously administered meropenem into the human aqueous humor and vitreous. Thirty patients about to undergo cataract surgery and fourteen patients about to undergo vitrectomy received a 2 g dose of meropenem before surgery. Specimens of aqueous humor or vitreous and blood were obtained intraoperatively and analyzed by high performance liquid chromatography (HPLC). The study was designed as a non-randomized prospective trial. Thirty min to 12 hr after administration, mean aqueous humor levels of 13.4 and 1.1 mg/l and vitreous levels between 8.94 and 1.08 mg/l were found, respectively. The peak concentrations are distinctly above the in vitro measured minimum inhibitory concentration of meropenem for 90% (MIC90) of almost all relevant gram-positive and gram-negative organisms, including Pseudomonas aeruginosa and Enterobacteriaceae. With regard to its broad spectrum, high antibacterial activity, and good penetration into ocular fluids, meropenem seems to be an alternative to currently used systemic drugs. Its usefulness in perioperative prophylaxis, as initial therapy after perforating or penetrating injuries, or in the therapy of bacterial endophthalmitis has yet to be proved.     

Transscleral and transcorneal iontophoresis of ketoconazole in the rabbit eye

The authors assessed the efficacy of transscleral and transcorneal iontophoresis of ketoconazole as a method of drug delivery to the aqueous humor, vitreous, and cornea of the rabbit eye. Transscleral iontophoresis (4-6 mAmps for 15 minutes) achieved peak ketoconazole concentrations in the aqueous 1 hour after treatment (10.2 micrograms/ml) and remained at fungicidal therapeutic concentrations for 8 hours; in the vitreous, a peak concentration of 0.1 microgram/ml occurred between 1 and 2 hours posttreatment. Transcorneal iontophoresis (1.5 mAmps for 15 minutes) achieved peak corneal concentration of 27.6 micrograms/ml and peak aqueous concentrations of 1.4 micrograms/ml, both 1 hour after iontophoresis. Fungicidal therapeutic drug concentrations were sustained for 2 hours both in the cornea and in the aqueous. These concentrations were compared with those obtained after subconjunctival injection (peak values): 0.8 microgram/ml in aqueous, 5.9 micrograms/ml in cornea, and 0.7 microgram/ml in vitreous, all within 1 hour of injection. Aqueous and corneal concentrations were significantly higher after transscleral and transcorneal iontophoresis than subconjunctival injection (P less than 0.05). Iontophoresis is proposed as an effective means of delivering high concentrations of ketoconazole to the anterior segment of the eye.     

Time course for prostaglandin synthesis by rabbit lens during endotoxin-induced ocular inflammation

Three hours to 14 days following the intravitreal injection of 10 ng of E. coli endotoxin into the vitreal chamber of one eye of the New Zealand white rabbit, ocular inflammation was evaluated by clinical and biochemical criteria and prostaglandins were measured in the intraocular fluids and in the incubation medium of the intact lens. Increased synthesis of PGE2 was detected for lenses from inflamed eyes beginning at 18 h post-endotoxin injection. Lenticular PGE2 synthesis remained above control levels for the duration of the time course. Lenses also exhibited increased PGF2 alpha synthesis, which began at 18 h and returned to control levels by day 7. At the times of peak production, aqueous humor PGE2 concentration correlated with lenticular PGE2 synthesis and with aqueous humor leukocyte number. No correlations were found for lenticular PGE2 vs. cell number, or vitreous humor PGE2 vs. aqueous humor PGE2. These results suggest that during ocular inflammation, aqueous humor PGE2 may be derived, at least in part, from the lens and leukocytes.     

Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate

PURPOSE: To study the dexamethasone concentration in aqueous humor, vitreous, and serum of patients after repeated topical application of dexamethasone disodium phosphate. DESIGN: Prospective nonrandomized comparative trial. PARTICIPANTS: Twenty phakic patients scheduled for a first vitrectomy. METHODS: All participants received dexamethasone disodium phosphate drops according to an application schedule intended to result in steady-state drug concentrations. Starting on the preoperative day, they received 1 drop of dexamethasone disodium phosphate (0.1%) every 1 hours until the time of vitrectomy (total, 10 or 11 drops). At night, ointment containing dexamethasone (0.3 mg/g) and gentamicin (5 mg/g) was administered once. From 7 AM on, the drop application schedule was resumed. At the start of the vitrectomy, samples were taken from the aqueous humor, vitreous, and blood. MAIN OUTCOME MEASURES: The dexamethasone concentrations in the aqueous humor, vitreous, and serum measured by radioimmunoassay. RESULTS: The mean dexamethasone concentrations in the aqueous humor, vitreous, and serum were 30.5 ng/ml (range, 7.1-57.7; standard deviation [SD] 15.0), 1.1 ng/ml (range, 0.0-1.6; SD 0.4), and 0.7 ng/ml (range, 0.0-1.2; SD 0.4), respectively. CONCLUSIONS: Compared with previously tested administration routes (peribulbar or subconjunctival injection or oral administration), the penetration of dexamethasone into the vitreous after repeated drop application is negligible. Despite the frequent dosing schedule, the dexamethasone concentration in the aqueous humor is far lower than after a subconjunctival injection with dexamethasone disodium phosphate. Systemic uptake is low.     

Ocular penetration of N-formimidoyl thienamycin (MK-787) and potentiation by dipeptidase inhibitor (MK-791)

N-formimidoyl thienamycin (MK-787) is a new beta-lactam with potent activity against both aerobic and anaerobic gram-positive and gram-negative bacteria. Its spectrum and activity suggest it may be useful in treatment of complicated intraocular infections. Its ocular penetration was studied in New Zealand white rabbits immediately before and after the third dose of 40 mg/kg administered intravenously at q6h intervals. Plasma, aqueous humor, and vitreous humor were obtained by direct aspiration, and antibiotic levels were assayed using an agar well diffusion method. MK-787 penetrated uninflamed intraocular fluids, including vitreous humor, although vitreous concentrations achieved (0.1-0.2 micrograms/ml) were significantly lower than the mean peak plasma (15 micrograms/ml) and aqueous concentrations (7 micrograms/ml). Nevertheless, the intraocular levels attained approached or exceeded the MIC90 for most sensitive organisms including some gram-negative bacilli important in bacterial endophthalmitis. When administered in combination with the renal enzyme inhibitor MK-791, plasma and aqueous concentrations of MK-787 were markedly potentiated, although vitreous concentrations were minimally affected. The potential usefulness of MK-787 in conjunction with MK-791 in the infected eye should be examined further in an animal model of bacterial endophthalmitis.     

Ocular trace metal kinetics and toxicology. I. The distribution of intravitreally injected 67Cu++ within intraocular compartments and its loss from the globe

Radioactive copper (67Cu++) was injected into the center of the vitreous body of rabbits. The relatively rapid initial loss of 67Cu from the vitreous was associated with its accumulation in intraocular tissues. At 24 hr, 20% of the injected 67Cu was found in the retina, representing the highest 67Cu concentration among all ocular tissues, and this high 67Cu concentration was maintained in this tissue throughout the 10-day observation period. Significant amounts of 67Cu were not detected in the aqueous humor at any time. About one-half of the injected 67Cu was lost from the whole globe in 5 days, but the remaining Cu was retained in the globe during the next 5 days. Eyes that received a large dose of CuSO4 in addition to the tracer showed decreased 67Cu activity in the retina and a slight increase in the aqueous humor. Endotoxin-induced ocular inflammation decreased the rate of 67Cu loss from the vitreous, reduced its accumulation by the retina, and increased 67Cu entry into the aqueous humor. It is concluded that 67Cu is retained in the vitreous and the globe due to its binding by, and/or uptake into, intraocular tissues, especially the retina. Cu does not effectively enter the anterior chamber from the vitreous, apparently due to its effective removal by the ciliary processes, thus ruling out the possibility of identifying the existence of Cu-containing intraocular foreign bodies in the posterior segment of the eye by analysis of Cu in the aqueous humor.     

Comparison of complications after Ahmed versus Baerveldt implant in glaucoma patients: one year follow-up

AIM: To compare surgical results of the Ahmed and Baerveldt implant procedures in glaucoma patients at 1y follow-up at Jakarta Eye Center (JEC) Eye Hospitals. METHODS: This cohort retrospective study was conducted on glaucoma patients aged ≥18y who had undergone Ahmed and Baerveldt implant surgery. Intraocular pressure (IOP), visual acuity, glaucoma medication, success rate, early and late postoperative complications, and the number of resurgeries were analyzed. RESULTS: A total of 351 eyes in the Ahmed group and 94 eyes in the Baerveldt group were included in this study. At 1y follow-up, the mean IOP was found to be significantly lower in the Baerveldt group (13±4.47 mm Hg) compared to the Ahmed group (15.02±5.73 mm Hg; P=0.025). Glaucoma medication was required in both the Ahmed and Baerveldt groups (58.92% vs 71.67%). Comparable success rate was found in both groups. The Ahmed group revealed a complete and qualified success of 86.82%, and failure of 13.17%. Similarly, the Baerveldt group showed complete and qualified success in 87.75% and failure in 12.25% cases. In the Ahmed group, 11.97% early complications, 26.06% late complications and 9.97% resurgeries were observed. In comparison, in the Baerveldt group, 23.40% early complications, 30.95% late complications and 11.70% resurgeries were observed. CONCLUSION: Both groups of glaucoma implants show significant IOP reduction, however, the Baerveldt implant group demonstrates greater IOP reduction with more failure rates and complications than the Ahmed implant group.     

Ocular pharmacokinetics of dacarbazine following subconjunctival versus intravenous administration in the rabbit

The authors assessed the ocular toxicity and pharmacokinetics of subconjunctivally and intravenously administered dacarbazine in New Zealand white rabbits. Nine rabbits received a subconjunctival injection of 5 mg (three animals), 10 mg (three animals) or 25 mg (three animals) of dacarbazine in 0.5 mL of sterile water; 10 mg was found to be a well-tolerated dose. This dose was given as a bolus to 42 other rabbits either subconjunctivally (21 animals) or intravenously (21 animals). In both groups the dacarbazine concentrations in the ocular humours, serum and urine were measured by means of high-pressure liquid chromatography at 0.5, 1, 2, 4, 8, 12 and 24 hours, three animals being assessed at each interval. The peak serum levels of the drug were similar with the two routes of administration. The mean peak dacarbazine levels in the aqueous humour and vitreous humour after subconjunctival administration were 250 to 380 times those achieved after intravenous administration. The bioavailability of the drug over 24 hours was 107 micrograms/h.mL in the aqueous and 34 micrograms/h.mL in the vitreous after subconjunctival administration, compared with 0.65 and 0.14 micrograms/h.mL respectively after intravenous administration. Our results provide a solid pharmacokinetic basis for considering subconjunctivally administered dacarbazine in the treatment of human ocular melanoma.     

Intraocular penetration of ketoconazole in rabbits.

We studied penetration of the antifungal agent ketoconazole into the cornea, aqueous humor, and vitreous of rabbits after topical, subconjunctival, and oral administration. The effect of debridement of corneal epithelium on penetration was also investigated. Ketoconazole levels in the cornea and aqueous humor were high after topical or subconjunctival administration, and increased markedly (especially in the cornea) if the corneal epithelium had been debrided before administration of the drug. For example, concentration of ketoconazole in the cornea 1 h after topical drug administration with or without complete corneal epithelial debridement was 44.0 +/- 10.1 and 1,391.5 +/- 130.0 micrograms/g, respectively. Drug levels in the vitreous were not detectable after topical or subconjunctival drug administration, but were improved slightly by prior epithelial debridement (8.3 and 0.12 micrograms/mL after 1 h, respectively). Orally administered ketoconazole resulted in high corneal concentrations (45.0 +/- 7.6 micrograms/g after 1 h) that were still substantial 24 h later (55.0 +/- 7.0 micrograms/g); levels in the aqueous were low.     

醋酸强的松龙滴眼后在兔眼内的分布

目的观察醋酸强的松龙短期和长期滴眼后在兔眼多种组织中的分布。方法用1g.L-1醋酸强的松龙滴眼液分1d内数次或连续29d长期滴兔眼,分别于滴眼后15min、30min、60min、120min和29d取材,高效液相色谱法测定角膜、房水、晶状体、玻璃体和血液中的激素含量。结果1g.L-1醋酸强的松龙滴眼液滴眼后兔眼不同组织和血液中的激素分布随时间而变化,无论短期或长期连续滴眼在角膜和房水中均获得较高的激素含量,血液和玻璃体中亦有少量进入。短期滴眼后,仅在晶状体赤道和前皮质有少量激素进入,长期局部滴眼时在晶状体各部位均有蓄积。结论1g.L-1醋酸强的松龙局部滴眼后易进入角膜和房水。此结果有助于了解眼部激素治疗和并发症发生的关系。     

卡铂兔眼结膜下及全身注射后眼内药物浓度的检测及临床意义

目的:全身静脉注射和眼结膜下注射化疗药物卡铂后检测眼内药物浓度,并比较两者的差别,为临床眼结膜下注射化疗药物卡铂治疗视网膜母细胞瘤提供理论依据。方法:分别用正常新西兰大白兔各4只,按18.7 mg/kg经静脉注射和10 mg/ml 0.5 ml右眼结膜下注射化疗药物卡铂,全身用药剂量是结膜下注射剂量的8倍。注射后1、2、3 h分别抽取房水和玻璃体样本0.2 ml,采用原子吸收光度法,用Z-8000型偏振塞曼原子吸收分光光度计检测房水及玻璃体中卡铂的含量。所得结果采用t检验进行统计分析。结果:全身用药后1、2、3 h房水和玻璃体卡铂含量分别为:140、330、180 ng/ml和20、40、17 ng/ml,结膜下注射后1、2、3 h房水和玻璃体卡铂含量分别为2 650、4 390、2 780 μg/ml和160、250、110 ng/ml。结果显示结膜下注药后眼内房水及玻璃体药物浓度明显高于全身用药后的眼内药物浓度,全身用药和结膜下用药各时段眼内药物含量分别作t检验,P<0.01,各组均有统计学显著性差异。结论:眼结膜下注射卡铂后眼内药物浓度明显高于全身注射后的眼内药物浓度。眼结膜下注射化疗药物这一方式可增加眼内药物浓度,有可能是一种有效的局部化疗方法。     

Antioxidant activity of aqueous and vitreous humor from the inflamed rabbit eye

The effects of aqueous and vitreous humors and plasma on the rate of auto-oxidation of a rabbit brain homogenate were measured. Both aqueous and vitreous humors from normal eyes increased, while plasma decreased the rate of oxidation in the homogenate. During endotoxin-induced ocular inflammation the copper (Cu) and iron (Fe) concentrations of both the aqueous and vitreous humors increased, most likely due to the influx of their plasma binding proteins, ceruloplasmin (Cu) and transferrin (Fe). As both proteins are known to be antioxidants, it was not surprising to find that the aqueous and vitreous humor from the inflamed eyes had significant antioxidant activity. This antioxidant activity correlated well with the concentrations of Cu and Fe in aqueous humor and Cu but not Fe in the vitreous humor throughout the time course of the inflammatory response. Thus, entry of plasma proteins through disrupted blood ocular barriers may function in protecting ocular tissues against the increased oxidation which occurs during inflammation.     

High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection.

PURPOSE: To determine the dexamethasone concentration in aqueous, vitreous, and serum of patients after a subconjunctival injection with dexamethasone disodium phosphate and to compare the effectiveness of a subconjunctival injection as a method of delivering dexamethasone into the vitreous with that of two previously tested routes: peribulbar injection and oral administration. METHODS: In a prospective study, 50 phakic patients who underwent a pars plana vitrectomy received a single subconjunctival injection with 2.5 mg of dexamethasone disodium phosphate, aqueous solution (after topical anesthesia and a subconjunctival injection with lidocaine) at varied intervals before surgery. An aqueous and a vitreous sample were taken from each patient, and serum samples were collected at multiple time points from nine of 50 patients. Dexamethasone concentrations were measured by radioimmunoassay. RESULTS: The estimated maximum dexamethasone concentration in the aqueous was 858 ng per ml at 2.5 hours after injection, and in the vitreous, 72.5 ng per ml at 3 hours. In serum, a mean maximum concentration of 32.4 ng per ml was measured at approximately 30 minutes after injection. CONCLUSIONS: Subconjunctival injection of 2.5 mg of dexamethasone disodium phosphate resulted in an estimated vitreous dexamethasone peak concentration three and 12 times higher, respectively, than after a peribulbar injection of 5 mg of dexamethasone disodium phosphate and an oral dose of 7.5 mg of dexamethasone. Thus, a subconjunctival injection is the most effective method of delivering dexamethasone into both the anterior and posterior segments of the eye. Systemic drug absorption is considerable and is of the same order of magnitude as after peribulbar injection.     

The disposition and bioavailability of 35S-GSH from 35S-GSSG in BSS PLUS in rabbit ocular tissues.

The purpose of this study was to evaluate the biodistribution and uptake of 35S-GSH into intraocular tissues following the administration of BSS PLUS containing 35S-GSSG by either an anterior chamber or intravitreal injection. This study evaluated the disposition and uptake of the 35S-radiolabel, the intracellular concentrations of 35S-GSH from extracellular 35S-GSSG, and the percentage of 35S-GSH to the total cellular GSH pool. Glutathione was analyzed by high-performance liquid chromatography (HPLC) using fluorescence detection after derivitizing the thiols in situ with monobromobimane. The effluent from the GSH peak was then collected for measurement of 35S-GSH. After an anterior chamber injection of 35S-BSS PLUS, 35S-radioactivity rapidly disappeared from the aqueous humor between 0.5 and 2 hours; corneal 35S-radioactivity remained constant over time. 35S-GSH was detected in the iris and ciliary body. However, in the cornea, 35S-GSH became the predominant radioactive thiol in the stroma, endothelium, and epithelium; the corneal stroma appeared to be a possible GSH reservoir for the adjacent corneal layers. After an intravitreal injection, 35S-radioactivity slowly decreased in the vitreous humor but was readily taken up by the tissues of the posterior segment, especially the retina and choroid, which showed the greatest concentrations of 35S-GSH of all tissues studied. The data from this study demonstrate that 35S-GSSG in BSS PLUS is metabolized and taken up by ocular cells and that 35S-GSH becomes incorporated into the intracellular GSH pool of ocular tissues.     

两种不同注射方法眼局部注射鼠神经生长因子后兔眼内药物分布

目的 观察兔玻璃体腔注射与球周注射~(125)I-神经生长因子(NGF)后眼部各组织药物含量分布.方法 45只家兔分别于左眼玻璃体腔(A组)和右眼球周(B组)注射~(125)I-NGF 30 μg/100μl.于注药后15、30 min,1、3、6、8、12、24、48 h取眼房水、玻璃体等眼内容物,角膜、巩膜等眼球外壁组织,虹膜睫状体、视网膜、脉络膜等眼球内壁组织进行γ-计数,计算~(125)I-NGF的含量.结果 A组药物在眼内容物及眼球内壁各组织弥散较快,玻璃体内含量呈梯度下降,其它眼内组织含量呈正态曲线变化;房水、虹膜睫状体、视网膜、脉络膜达峰值时间均为给药后3 h,巩膜、角膜分别为6、8 h;B组眼内各组织药物含量呈正态曲线变化,药物达眼内峰值时间较慢,除房水在给药后3 h达峰值,其他组织均在6 h达峰值;A组各组织~(125)I-NGF峰值含量也明显高于B组;A组除玻璃体直接注射导致高药物含量外,视网膜药物含量最高.结论 玻璃体腔注射~(125)I-NGF较球周注射更能在眼内各组织达到高药物含量.