Noninvasive monitoring of intraocular pharmacokinetics of daunorubicin using fluorophotometry

Purpose. Daunorubicin is a cytotoxic drug, which, in nontoxic doses, is effective in preventing cellular proliferation in experimental vitreoretinopathy. We studied dose and clearance of daunorubicin in various ocular tissues using fluorophotometry techniques. Methods. In vitro tests: The emission of fluorescence from the daunorubicin solution having a concentration range of 0.1 to 10 g/mL in phosphate buffer was measured using an excitation wavelength range of 489 ± 10 nm. The emission of fluorescence was measured at 514 nm; the linearity of the response was determined using linear regression analysis. There is a fluorescence peak of daunorubicin at 485 nm. The validity and reproducibility of the method were examined. In vivo tests: The rabbits were randomized into three groups and daunorubicin concentrations of 4, 6, or 8 g/mL were injected into the vitreous. Fluorophotometry scanning from the retina to the anterior chamber was performed with a commercially available fluorophotometer at various times up to 48 hours after injection to quantify fluorescence emission of daunorubicin. Results. The standard curve of fluorescence versus concentration of daunorubicin was linear in the range of 0.1 to 8 g/mL. It was sensitive up to 0.1 g. The daunorubicin time concentration profile showed a dose response relationship over the 48-hour period studied. The half-life of daunorubicin in the vitreous was about 5 hours. Conclusion. We performed fluorophotometry using a fluorophotometer whose exciter emits light at 489 nm, which is very close to an absorption peak of daunorubicin. These two values are close enough to obviate the need for modifying the commercial fluorophotometer. Therefore the concentration of daunorubicin in the vitreous cavity can be measured noninvasively.Supported in part by U.S. Public Health Service grants EY07541, EY08137, and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA.     

Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration

OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively. CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.     

Aqueous and vitreous penetration of levofloxacin after topical and/or oral administration

PURPOSE: To investigate the aqueous and vitreous penetration of levofloxacin, the drug was administered topically and/or orally to patients undergoing vitrectomy. METHODS: Thirty-six patients undergoing initial vitrectomy with phacoemulsification and aspiration (PEA) were enrolled, and were divided randomly into three groups. Group 1 was treated with topical application of levofloxacin (three times on the day before surgery and seven times on the day of surgery), Group 2 received oral administration of levofloxacin (200 mg twice on the day before surgery and 200 mg at 3 hours before surgery), and Group 3 received both topical and oral levofloxacin according to the above schedules. The concentration of levofloxacin was measured in aqueous humor and vitreous fluid samples obtained during surgery. RESULTS: In Groups 1, 2, and 3, the mean levofloxacin concentration in aqueous humor was 0.765+/-0.624 micro g/mL, 1.279+/-0.440 micro g/mL, and 1.823+/-0.490 micro g/mL, respectively, while the mean levofloxacin concentration in vitreous fluid was <0.02 micro g/mL, 1.455+/-0.445 micro g/mL, and 1.369+/-0.530 micro g/mL, respectively. CONCLUSIONS: Oral administration of levofloxacin at a dose of 400 mg/day was sufficient for the prophylaxis of ocular infections, because the drug concentrations in both aqueous humor and vitreous fluid were higher than the MIC90 values for major ocular pathogens. Topical application of levofloxacin achieved adequate drug levels in aqueous humor, but not in vitreous fluid, while combined topical and oral administration had an additive effect on the drug concentration in aqueous humor.     

Effect of piroxicam on the blood-retina barrier in experimentally induced diabetes in rats

The effect of piroxicam on the blood-retina barrier was evaluated in rats with experimentally induced diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ). Diabetic rats were divided into two equal groups: those treated with piroxicam, a long-acting platelet inhibitor, and an untreated control group. Vitreous fluorophotometry (VFP) was performed both before and two weeks after induction of diabetes and piroxicam intake. Streptozocin-induced diabetes caused an alteration in the blood-retinal barrier evidenced by an increase in vitreous fluorescein concentration in diabetic rats compared with normal rats. Piroxicam intake did not lead to significant change in vitreous fluorescein concentrations. However, the examination had to be terminated at two weeks because of cataract formation. The piroxicam treated group showed less incidence of lens opacity formation (59.1% compared to 81.8% in the untreated group, p = 0.0006). Piroxicam administration appears to protect the diabetic rat eye against lens opacification.This work was supported in part by U.S. Public Health Service Grants EY02377, EY07541 and EY08137 from the National Eye Institute, National Institutes of Health, Bethesda, MD and by the Juvenile Diabetes Foundation International and Pfizer, Inc.     

Relationships between vitreous levels of soluble receptor for advanced glycation end products (sRAGE) and renal function in patients with diabetic retinopathy

Purpose

We investigated the relationship between vitreous levels of soluble receptor for advanced glycation end products (sRAGE) and vascular endothelial growth factor (VEGF) and renal function, and correlations between vitreous sRAGE levels and proliferative diabetic retinopathy (PDR) activity.

Methods

We examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (eight patients in the non-PDR [NPDR] group and 25 in the PDR group). Serum creatinine levels and estimated glomerular filtration rate (eGFR) were measured and classified according to the chronic kidney disease (CKD)-staging method. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify vitreous sRAGE and VEGF levels.

Results

Vitreous sRAGE levels were significantly higher in PDR group compared to NPDR group (p = 0.00003). Vitreous sRAGE levels were significantly higher in patients with CKD stage 5 (end-stage renal failure or hemodialysis) than in patients with CKD stage 1 or 2 (p < 0.01) and 3 or 4 (p < 0.05), and were significantly correlated with eGFR (r = ? 0.490, p = 0.007) and creatinine levels (r = 0.484, p = 0.006). Within the PDR group, patients with low (<27 pg/mL) sRAGE levels required repeat vitreous surgeries for early postoperative vitreous hemorrhage significantly more frequently than those with high (≥27 pg/mL) sRAGE levels (p = 0.0067).

Conclusions

Vitreous sRAGE levels were significantly correlated with renal function, and low vitreous sRAGE levels in patients with PDR were associated with postoperative vitreous hemorrhage. Vitreous sRAGE may be a useful biomarker for renal dysfunction associated with diabetic retinopathy.

     

Vitreal penetration of oral moxifloxacin in humans

PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral administration. DESIGN: Prospective, nonrandomized clinical series. METHODS: Twenty-four patients (mean age = 62.8 years) undergoing elective pars plana vitrectomy were assigned to a dosing group: control (n = 3), which received no medication; single-dose (n = 11), which received one 400 mg oral dose of moxifloxacin 3 hours before surgery; and five-dose (n = 10), which received one 400 mg dose on each of the 4 days preceding surgery and a fifth dose 3 hours before surgery. Vitreous samples were obtained and analyzed. RESULTS: Control, below quantifiable levels; single-dose, 0.572 +/- 0.239 microg/mL; and five-dose, 1.200 +/- 0.645 microg/mL. CONCLUSIONS: Five doses of oral moxifloxacin lead to higher intravitreal drug concentrations than single-dose administration. Both regimens, however, achieve levels that exceed the MIC90 of many bacteria implicated in postoperative endophthalmitis.     

Evaluation of vitreous levels of gatifloxacin after systemic administration in inflamed and non‐inflamed eyes

Purpose: This study aimed to evaluate the human vitreous penetration of gatifloxacin in inflamed and non‐inflamed eyes after oral administration. Methods: Vitreous penetration of single‐dose (400 mg) oral gatifloxacin was evaluated in patients (n = 33) undergoing vitreous tap during the standard procedure for intravitreal antibiotic injection for acute postoperative endophthalmitis at various time‐points. Vitreous penetration of 400 mg oral gatifloxacin was evaluated in the non‐inflamed eyes of patients (n = 33) undergoing pars plana vitrectomy at similar time‐points. The study was extended to evaluate the vitreous penetration of single‐dose oral (800 mg) gatifloxacin at a single time‐point in inflamed (n = 10) and non‐inflamed (n = 11) eyes. Results: After 400 mg oral gatifloxacin, inflamed eyes showed mean vitreous concentrations of 0.58±0.19μg/ml, 1.33±0.33 μg/ml and 1.30 ± 0.23 μg/ml at 2, 4 and 6 hours, respectively. The levels reached at 2 and 4 hours were found to be significantly increased compared with those in non‐inflamed eyes. At the 800‐mg dose, 4‐hour vitreous levels in inflamed and non‐inflamed eyes were 1.57 ± 0.3 μg/ml and 1.42 ± 0.24 μg/ml, respectively. Although the increased dose of gatifloxacin elevated plasma concentration, it failed to raise vitreous levels significantly higher than the 400‐mg dose at the 4‐hour time‐point. Conclusions: Orally administered gatifloxacin achieves therapeutic levels in both inflamed and non‐inflamed human eyes with a spectrum covering the bacterial species most frequently involved in the various causes of endophthalmitis. However, the levels achieved were below the MIC₉₀ for Pseudomonas aureginosa and Enterococcus.     

Human vitreous levels of cefamandole and moxalactam

We gave 2-g intravenous doses of either cefamandole or moxalactam to 22 patients before vitrectomy. At 1 1/2 to 2 1/2 hours after administration, cefamandole vitreous concentrations varied from 0.36 to 2.05 micrograms/ml (mean, 0.94 micrograms/ml). Individual levels above the minimum inhibitory concentration of cefamandole for 90% (MIC90) of Staphylococcus aureus were found in five of 11 patients. Levels above the MIC90 for S. epidermidis were found in only two of 11 samples. Vitreous concentrations above the MIC90 of cefamandole for common gram-negative pathogens were found in only two patients. Moxalactam concentrations in the vitreous varied from 1.1 to 4 micrograms/ml 30 minutes to six hours after administration. These levels were not above moxalactam's MIC90 for S. aureus or S. epidermidis but were many times higher than the MIC90 of moxalactam for Enterobacteriaceae excluding Pseudomonas.     

Bioavailability of microsphere-entrapped cyclosporine A in the cornea and aqueous of rabbits

Extended release of immunosuppressive drugs and sustained drug levels are desirable for the treatment of corneal graft rejection and other ocular immune disorders. This experiment was conducted with biodegradable microspheres containing cyclosporine A to assess their suitability for achieving this goal. Microspheres containing cyclosporine A were prepared using a solvent evaporation process. A mixture of poly (lactic) and poly(glycolic) acid polymers (50: 50) and cyclosporine A was dissolved in a mixture of chloroform and acetone. The solution was then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. The final assayed concentration of cyclosporine A was 15.38 mg/mL. A 0.13 mL aliquot (2.0 mg) of the suspension of the microspheres was injected subconjunctivally in 24 eyes of white New Zealand rabbits. The concentration of cyclosporine A in the aqueous and cornea was measured at 6, 12, 24, 48, 72, and 144 hours after injection (n=4 for each group). Corneal levels of cyclosporine A ranged from 2392±70 ng/mL at 6 hours to 1297±459 ng/mL at 144 hours. The aqueous levels ranged from 110±0 ng/mL at 6 hours to 62±11 ng/mL at 144 hours. These data indicate that a microsphere drug delivery system is an effective means of delivering cyclosporine A to the cornea and anterior chamber, and may provide an alternative for the treatment of ocular immune disorders.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA.     

Calcein: A new dye for evaluation of the blood-retinal barrier by fluorophotometry

A vitreous fluorophotometry study was performed on rabbits to compare the characteristics of carboxyfluorescein and calcein with those of sodium fluorescein. Our results demonstrated that carboxyfluorescein and calcein attained mid vitreous concentrations similar in magnitude to fluorescein approximately one hour after injection of the dye. As long as three to four hours after injection of the dye, the mean fluorescence levels of calcein in the chorioretina were much higher than those of sodium fluorescein and carboxyfluorescein. These results point out that calcein has potential experimental and clinical use as a probe of the blood-ocular barrier as well as in experimental and clinical angiography of the fundus.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA     

Intravitreal antibiotic injection and vitrectomy in acute bacterial endophthalmitis.

Two days after an unplanned extra-capsular cataract extraction with sector iridectomy, a patient showed typical signs of bacterial endophthalmitis. Vitreous and aqueous were aspirated for culture, and gentamicin and dexamethasone were injected. Twenty-four hours later, after isolation of Staphylococcus epidermidis, a vitrectomy to remove the central vitreous was done. Postoperatively, vision progressively improved; at the last review nine months after vitrectomy, visual acuity was 20/50.     

Perfluorooctylbromide (PFOB) as a vitreous substitute in non-human primates

We evaluated the toxicity of perfluorooctylbromide in the primate eye as a short-term postoperative vitreous substitute. Four eyes of 4 African green monkeys underwent complete vitrectomy and vitreous replacement with 1.5–2.0 ml of PFOB. One additional animal received BSS as a control vitreous substitute in one eye. Animals were examined twice weekly for clarity and consistency of the vitreous replacement substance. Anterior segment and lenses remained clear in all eyes, although in the immediate postoperative period one eye became inflamed and had a culture-negative vitritis. The other eyes showed a minimal anticipated postoperative vitreous inflammation. Emulsification of the PFOB began within 3 days of injection and progressed up to 3 weeks, precluding fundus examination and fluorescein angiography after 2 weeks. Eyes were enucleated and light microscopy performed at 2 days, 10 days, 33 days, and 45 days. No toxic effects to the retinal cells were detectable by histological examination, but perivasculitis of retinal vessels was noted at 45 days. Indirect examination was normal up to 10 days; thereafter, the fundus view was obscured by the emulsified PFOB. Because of cellular migration into the vitreous cavity and retinal perivasculitis, observed histologically, PFOB seems most suitable for intraoperative rather than postoperative use.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 and NEI1F32EY06193-03 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA.     

Concentration of acute phase factors in vitreous fluid in diabetic macular edema

Purpose

Diabetic retinal maculopathy is associated with acute and chronic local inflammation. We measured the concentrations of acute phase factors in vitreous fluid of patients with diabetic macular edema (DME) and examined their relations to visual acuity and central retinal thickness (CRT) both before and after vitrectomy.

Study design

Retrospective.

Methods

Vitreous fluid was collected during vitreoretinal surgery from 19 patients with DME and 12 control subjects with epiretinal membrane. The concentrations of acute phase factors (α2-macroglobulin, haptoglobin, C-reactive protein, serum amyloid P and A, procalcitonin, ferritin, tissue plasminogen activator, fibrinogen) and vascular endothelial growth factor (VEGF) were measured with multiplex assays. CRT of macular edema was measured by optical coherence tomography (OCT).

Results

The levels of serum amyloid P, procalcitonin, ferritin, and fibrinogen in vitreous fluid were increased in DME patients compared with control subjects. The levels of procalcitonin and fibrinogen in DME patients were inversely correlated with visual acuity both before and 3 months after vitrectomy but not 6 months postsurgery. The concentrations of these four factors were not correlated with either CRT or the vitreous levels of VEGF in DME patients.

Conclusion

Acute phase factors may contribute to local inflammation in DME and may therefore influence disease progression.

     

Vitreous concentrations of triamcinolone acetonide in human eyes after intravitreal or subtenon injection

PURPOSE: To compare vitreous concentrations of triamcinolone acetonide (TA) achieved by prior therapeutic intravitreal and subtenon injections. DESIGN: Interventional case series. METHODS: Vitreous samples were collected from patients who required vitreous surgery, six having received a subtenon injection of TA and another six, an intravitreal injection. Vitreous concentrations of TA were measured by high-performance liquid chromatography. RESULTS: Vitreous concentrations of TA after intravitreal injection were 1.22 +/- 0.24 mug/ml, significantly higher than those after subtenon injection (<0.001 mug/ml, P = .003). Vitreous concentrations of TA after subtenon injection and TA-assisted vitrectomy performed in a few patients to visualize the transparent vitreous gel were 0.20 +/- 0.11 mug/ml, an intermediate amount between these two groups. CONCLUSION: Much higher vitreous concentrations of TA after intravitreal injection than subtenon injection may accelerate therapeutic effect when intravitreal injections are given to reduce macular edema. Subtenon injections of TA may act via the sclera as opposed to the vitreous.     

Determination of aqueous and vitreous concentration of moxifloxacin 0.5% after delivery via a dissolvable corneal collagen shield device

PURPOSE: To determine the penetration of moxifloxacin 0.5% in the human aqueous and vitreous when delivered by a presoaked collagen shield. SETTING: University-based clinical practice. METHODS: Moxifloxacin 0.5% was administered before vitrectomy surgery in 10 patients using a 24-hour dissolvable cross-linked corneal collagen shield delivery device. Aqueous and vitreous samples were obtained after the shield was placed for 4 hours in the first 5 patients and for 24 hours in the second 5 patients. Assays were performed using high-performance liquid chromatography. RESULTS: Delivery of moxifloxacin via a collagen shield revealed a mean aqueous concentration of 0.30 microg/mL +/- 0.17 (SD) 4 hours after placement (n = 5). Vitreous levels at 4 hours and aqueous and vitreous levels at 24 hours were negligible using this route of administration. Peak aqueous moxifloxacin levels occurred soon after shield placement. This is when high concentrations of moxifloxacin are most needed to clear the aqueous of bacteria. The minimum inhibitory concentration at which 90% of the isolates were inhibited for organisms commonly responsible for endophthalmitis was exceeded in the 4-hour aqueous group. Negligible concentrations were detected at 24 hours. CONCLUSIONS: Although aqueous moxifloxacin levels achieved through the use of a collagen shield delivery device are lower than via topical drops, there are several advantages to this route of delivery that make it appealing in the immediate postoperative period. Future studies will be needed to define precisely the role of fourth-generation fluoroquinolones and presoaked collagen shields in the prophylaxis or management of intraocular infections.     

Clearance of intravitreal voriconazole

Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits. METHODS: Intravitreal injections of 35 microg/0.1 mL voriconazole were administered to rabbits. Vitreous and aqueous humor levels of voriconazole were determined at selected time intervals (1, 2, 4, 8, 16, 24, and 48 hours), and the in vitreous half-life was calculated. Four to six eyes per time point after injection were enucleated and immediately stored at -80 degrees C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals. Voriconazole concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography (HPLC). RESULTS: The concentration of intravitreal voriconazole at various time points exhibited exponential decay with a half-life of 2.5 hours. The mean vitreous concentration was 18.912 +/- 2.058 microg/mL 1 hour after intravitreal injection; this declined to 0.292 +/- 0.090 microg/mL at 16 hours. The mean aqueous concentration was much lower and showed a decline from 0.240 +/- 0.051 microg/mL at 1 hour to undetectable levels 8 hours after injection. CONCLUSIONS: Vitreous concentrations achieved during the first 8 hours were greater than the previously reported minimum inhibitory concentrations (MICs) of organisms most involved in fungal endophthalmitis. A rapid decline of intravitreal concentration suggests that supplementation of intraocular voriconazole to maintain therapeutic levels may therefore be required in clinical settings. Further studies are needed to determine the elimination rate of voriconazole after intravitreal injection in humans.     

Use of vancomycin in vitrectomy infusion solution and evaluation of retinal toxicity

The retinal toxicity of vancomycin in infusion solution used in vitrectomy and lensectomy was investigated in rabbit eyes by means of electroretinography and histologie study (light microscopy). Concentrations of 8g/ ml, 16g/ml, and 32g/ml of vancomycin in balanced salt solution caused no abnormal ERG or histologic changes. However, ERG amplitude depression and abnormal histologie changes occurred when the concentration of 100g/ml of vancomycin was used.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD.     

Shiva-1: in vitro and in vivo tests of the effects of a novel,synthetic, lytic peptide on ocular cells

An investigation was undertaken to determine the toxicity of an intravitreal injection of a novel peptide drug, Shiva-1, in rabbits. The drug, a synthetic peptide modeled after lytic peptides secreted by certain insects, has antiproliferative and antibacterial properties. Initial in vitro experiments showed that the drug, at a concentration of 100 M, was toxic to both Y-79 retinoblastoma cells and human retinal pigment epithelial cells. A wide range of doses (6–1200 g) was injected into the rabbit vitreous in an attempt to determine the maximum tolerated dose. Retinal toxicity was evaluated clinically, by electroretinography, and by light microscopy. Some localized toxicity was evident at 200 g; all doses of 240 g and above were toxic. While the drug appears to exhibit a narrow range between effective and toxic doses, the results suggest that this and other peptides of similar design merit further investigation for the treatment of proliferative and infectious diseases of the eye.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, the National Institutes of Health Services, Bethesda, MD, USA     

Vitreoretinal juncture over retinal vessels

Summary Previous studies have attributed changes in the retinal surface over or adjacent to large superficial retinal vessels to a variety of conditions, the most common being anomalous vitreoretinal attachments. The fundamental nature of the lesions and their pathogenesis, however, has remained controversial. The present study was undertaken to categorize the ultrastructural alterations of the vitreoretinal juncture over retinal vessels in the posterior fundus of man, and to clarify the relationship of these fundamental changes to clinically significant lesions in this region.Results show no difference in vitreoretinal, or more specifically vitreolaminar attachments over vessels when compared with adjacent regions. The cause of the more significant anomalies, notably surface breaks and their sequelae, is apparently multifactorial and related to a sequence of events. Initially three events predispose to or cause small surface breaks: developmental thinning of the inner limiting lamina; subsurface retinal degeneration; and transmigrating macrophages. These small surface breaks, when complicated by vitreous incarceration or by simple epiretinal membrane formation, can during posterior vitreous detachment cause peeling of the retinal surface, and the resulting large surface breaks may in turn provoke more complex proliferative lesions of the vitreoretinal juncture.This investigation was supported in part by U.S. Public Health Service research grants EY 00331, EY 01090, and EY 00725 from the National Eye Institute, National Institutes of Health     

Aqueous and vitreous penetration of levofloxacin after oral administration

OBJECTIVE: To investigate the penetration of levofloxacin, an optical S-(-)isomer of ofloxacin, into the aqueous and vitreous humor after oral administration. DESIGN: Randomized, clinical trial comparing tissue levels of levofloxacin after one or two doses 12 hours apart. PARTICIPANTS: Forty-five patients undergoing initial vitrectomy between February 1997 and June 1997 at the UIC Eye Center. METHODS: Aqueous, vitreous, and serum samples were obtained and later analyzed from 45 patients after oral administration of 1 500-mg tablet (group 1, 22 patients) or 2 500-mg tablets (group 2, 23 patients) 12 hours apart before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and serum concentrations of levofloxacin (micrograms/milliliter). RESULTS: Group 1 achieved mean aqueous, vitreous, and serum levels of 0.59 +/- 0.48 microg/ml, 0.32 +/- 0.34 microg/ml, and 4.34 +/- 3.59 microg/ml, respectively. Group 2 achieved mean aqueous, vitreous, and serum levels of 1.90 +/- 0.97 microg/ml, 2.39 +/- 0.70 microg/ml, and 8.02 +/- 3.14 microg/ml. CONCLUSIONS: Mean inhibitory aqueous and vitreous MIC90 levels were achieved against a majority of ocular pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae (vitreous), Bacillus cereus (vitreous), Haemophilus influenzae, Moraxella catarrhalis, and most gram-negative aerobic organisms except Pseudomonas aeruginosa after two doses given 12 hours apart. Mean MIC90 levels were obtained in the vitreous for a majority of pathogens responsible for traumatic, postoperative, or bleb-related endophthalmitis.