Ocular penetration of cefazolin in humans and rabbits after subconjunctival injection

We determined the clinical potential of cefazolin by assaying aqueous samples for levels of aqueous penetration of cefazolin in humans and rabbits after subconjunctival injection. Cefazolin is a broad spectrum antiotic that appears to penetrate aqueous humor in bactericidal concentrations after subconjunctival injection and may serve as a useful alternative in patients sensitive to other antibiotics.     

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 tri-tetracyclines after parenteral and subconjunctival administration

Summary Methacycline, doxycycline, and oxytetracycline were administered to rabbits in the form of tri-tetracycline complexes and pyrrolidinomethyloxytetracycline by i.v. or subconjuntival injection. Antibiotic levels in the aqueous humour proved to be highest after tri-methacycline when the substances were administered by the i.v. route and after administration of tri-doxycycline when they were given subconjunctivally. Administration of tri-oxytetracyclines resulted in higher aqueous humour levels than pyrrolidinomethyloxytetracycline after both i.v. and subconjunctival administration. Chemosis was never observed.

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Zusammenfassung Kaninchen wurden Methacyclin, Doxycyclin und Oxytetracyclin in der Form von Tri-tetracyclin Komplexen und Pyrrolidinomethyloxytetracyclin intravenös oder subconjunctival verabreicht. Der höchste Kammerwasserspiegel wurde nach Tri-methacyclin erreicht, wenn die Applikation intravenös erfolgte und nach Tri-doxycyclin im Falle von subconjunktivaler Verabreichung. Die intravenöse oder subconjunktivale Application von Tri-oxytetracyclin gab höhere Kammerwasserkonzentrationen als Pyrrolidinomethyloxytetracyclin. Chemosis war nie zu beobachten.

     

Intraocular distribution of 70-kDa dextran after subconjunctival injection in mice

PURPOSE: To investigate the intraocular distribution kinetics of 70-kDa dextran after subconjunctival injection. METHODS: The right eye of 15 mice received a single subconjunctival injection of a 1.5-microL solution of 0.25% 70-kDa tetramethylrhodamine-dextran (TMR-D). The distribution of fluorescent labeling in eye sections was examined by fluorescence microscopy at 0.25, 1, 4, 24, or 72 hours after the injection. The brightness and homogeneity of fluorescence in the sclera, choroid, and retina were scored near the injection site, on the side of the globe opposite the injection site, and adjacent to the optic nerve head. Fluorescence intensity within the sclera and choroid adjacent to the optic nerve was assessed quantitatively by imaging densitometry. RESULTS: TMR-D readily diffused transsclerally and dispersed throughout a large portion of the sclera, uvea, and cornea. Shortly after the injection, homogenous fluorescence was observed in the sclera and choroid on the same meridian as that of the injection site. This fluorescence gradually decreased in intensity with distance from the injection site. At the opposite meridian, fluorescence in the choroid was more intense than in the adjacent sclera and could be traced up to the ciliary muscle. TMR-D was also observed in the retinal and optic nerve vessels. The intensity of scleral and choroidal fluorescence adjacent to the optic nerve reached a maxima at 1 hour, and then decreased slowly, with half-lives of approximately 16 and 100 hours, respectively. Visible fluorescence was maintained at least until 72 hours in the sclera, choroid, iris, and cornea. Specific fluorescent labeling was never found in the contralateral eyes. CONCLUSIONS: Macromolecular 70-kDa dextran can be readily delivered to the mouse retina and uveal tissues by subconjunctival injection through transscleral diffusion, local hematogenous spread, and possibly movement through the uveoscleral outflow pathway. Subconjunctival injection may be a useful approach for delivering macromolecules to the retina and uvea.     

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.     

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.     

Intraocular penetration of fosfomycin in man and rabbits

The intraocular distribution of fosfomycin was studied in 32 patients undergoing cataract surgery and or vitrectomy and in 8 rabbits after experimental infection of one eye by Staphylococcus aureus. In subjects perfused with 4 g of fosfomycin, concentrations ranged from 14 to 18.8 mg/l in aqueous humour (AH) and from 8 to 12.5 mg/l in vitreous fluid (VF) between 1 and 6 hours after the end of the perfusion; these levels were higher than MICs for 80-90 per cent of bacteria found in endophthalmitis. In rabbits the concentration in infected eyes with respect to healthy eyes was found to be from 2.5 to 5 times in AH and from 4.9 to 19.2 times higher in VF. Therefore fosfomycin in association with third generation cephalosporins (ceftriaxone) or with new quinolones can be recommended in the prevention and early treatment of endophthalmitis.     

Intraocular and plasma kinetics of tenoxicam in rabbits

Non-steroidal anti-inflammatory drugs (NSAID) represent potentially useful agents in the treatment of a number of ocular pathologies, but their intraocular penetration and distribution have not yet been reported. With the aim of clarifying this point, we evaluated the concentrations of the well known NSAID, tenoxicam, in the aqueous and vitreous humors of rabbits treated i.m. with the drug (7 mg/kg). The tenoxicam kinetics in these ocular fluids followed that in plasma with the time-to-peak shifted to higher values in the vitreous (1 h) as compared to that in the aqueous and plasma (40 min). AUC was also higher in the vitreous (10.4 g· h/ml) than in the aqueous humor (2.8 g·h/ml).     

Lidocaine hypersensitivity after subconjunctival injection

CASE REPORT: We report a rare case of hypersensitivity in a 63-year-old man who received subconjunctival lidocaine, cefazolin, and gentamicin for corneal abscess. Significant palpebral swelling and erythema were observed several hours after the injection. Nine months later, he received subconjunctival lidocaine, vanco-mycin, and ceftazidime for a new corneal abscess. After several hours, the eyelids were red and swollen, with mild blistering and scaling of the cheek. Two patch tests for lidocaine were negative. During follow-up, lateral tarsorrhaphy was performed under local anesthesia with lidocaine; erythema and swelling of eyelids and cheek appeared, resolving after several days. COMMENTS: Sensitivity to lidocaine can appear after subconjunctival injection. Patch tests may be negative, but the allergy suspected by the recurrence of clinical signs after rechallenge with lidocaine. Ester anesthetics can be used for local anesthesia.     

Comparison of intraocular penetration level of cefuzonam sodium and cefotiam after intravenous and subconjunctival injection

We investigated the intraocular penetration of a new Cephem type antibiotic: Cefuzonam sodium (CZON) following intravenous and subconjunctival injection. CZON was administered to 28 eyes in 26 patients by 1 g intravenous injection (IV) and to 11 eyes in 10 patients by 20 mg/0.2 ml subconjunctival injection (SCI). The penetration level of CZON by the IV method was from less than 0.0025-3.35 micrograms/ml into aqueous humor, from less than 0.0025-0.315 microgram/mg into iris tissue and 2.7-157.5 micrograms/ml into serum. The penetration level of CZON by the SCI method was from less than 0.0025-12.8 micrograms/ml into aqueous humor, from less than 0.0025-0.0426 microgram/mg into iris tissue and 1.03-18.5 micrograms/ml into serum. The penetration level of CZON into aqueous humor by SCI was higher than by IV administration. In comparison with the penetration level of CZON and Cefotiam (CTM), both aqueous humor and serum levels of CTM were higher than those of CZON. These results suggested that therapeutic levels in aqueous humor effective against gram-positive and gram-negative pathogens were achieved with the 1 g IV and 20 mg SCI of CZON. However levels effective against Staphylococcus epidermidis were only erratically attained.     

Intraocular acyclovir levels after subconjunctival and topical administration.

Substantial levels of acyclovir were detected in the aqueous and vitreous of New Zealand rabbits at various time intervals following subconjunctival injection. Intravitreal penetration of acyclovir after topical application was poor.     

Intraocular pressure reduction after subconjunctival mitomycin-C in absolute glaucomatous eyes

This study investigated the intraocular pressure (IOP) lowering effect of subconjunctival injection of mitomycin-C in human eyes blinded by glaucoma. Twenty eyes received injection of 1 mg of mitomycin-C and were followed up for 2 months. A statistically significant decline in IOP was observed until day 30 in all patients. The IOP-lowering effect of 1 mg of subconjunctivally injected mitomycin in patients with intractable glaucoma appears to be temporary.