Population pharmacokinetics of marbofloxacin in aqueous humor after intravenous administration in dogs

OBJECTIVE: To evaluate, by use of population pharmacokinetics, the disposition of marbofloxacin in the aqueous humor after IV administration in dogs and identify its potential usefulness in the prophylaxis and treatment of intraocular infection. ANIMALS: 63 dogs. METHODS: Dogs received a single dose of marbofloxacin (2 mg x kg(-1), IV) at various time intervals before cataract surgery. Aqueous humor and blood samples were collected at the beginning of surgery. Marbofloxacin concentrations were measured by high-pressure liquid chromatography. Data were analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg x kg(-1) IV. Pharmacodynamic surrogate markers and measured aqueous humor concentrations were used to predict in vivo antimicrobial activity. RESULTS: A maximum marbofloxacin concentration of 0.41 +/- 0.17 microg x mL(-1) was reached in the aqueous humor 3.5 hours after IV administration. In the post-distributive phase, marbofloxacin disappeared from aqueous humor with a half-life of 780 minutes. The percentage penetration into the aqueous humor was 38%. Predictors of antimicrobial effects of marbofloxacin (2 mg x kg(-1), IV) indicated that growth of the enterobacteriaceae and certain staphylococcal species would be inhibited in the aqueous humor. Marbofloxacin administered IV at a dose of 5.5 mg x kg(-1) would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections.     

Ocular penetration of oral doxycycline in the horse

OBJECTIVE: To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation. RESULTS: Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected in the aqueous on days 1 and 5, nor could it be detected in the vitreous on day 1. On day 5, the mean vitreous doxycycline concentration was 0.17 +/- 0.04 microg/mL at 2 h after drug administration. CONCLUSIONS: Repeated oral administration of doxycycline in the horse resulted in steady state serum concentrations of < 1 microg/mL; however, it did not result in appreciable concentrations of drug in the aqueous and vitreous in normal eyes.     

Ocular parameters related to drug delivery in the canine and equine eye: aqueous and vitreous humor volume and scleral surface area and thickness

OBJECTIVE: To measure the ocular surface area, scleral thickness, and the aqueous and vitreous humor volumes in the canine and equine eye. Animals studied Fourteen canine and 16 equine cadaver eyes. PROCEDURE: Eyes were measured either fresh or following fixation in formalin. Ocular surface area was calculated using the fluid displacement method. Globes were hemisected and aqueous and vitreous humor were collected and quantitated. Scleral thickness was measured by digital caliper, by image projection, and by ultrasonic biomicroscopy (UBM). RESULTS: Mean +/- standard deviation (SD) scleral surface areas in canine and equine eyes were 12.87 +/- 2.24 and 57.23 +/- 5.63 cm2, respectively. Mean +/- SD aqueous humor volume was 0.77 +/- 0.24 in the dog and 3.04 +/- 1.27 mL in the horse. Mean vitreous humor volume was 1.7 +/- 0.86 mL for the canine eye and 26.15 +/- 4.87 mL for the equine eye. In canine and equine eyes, the sclera was thinnest at the ocular equator: 0.34 +/- 0.13 mm (canine) and 0.53 +/- 0.1 (equine). There were no significant differences between the direct caliper and projected thickness measurements or differences between measurements in the superior, inferior, nasal, and temporal quadrants of the eye. Scleral thickness in fresh tissue was greater than in fixed tissue at most sites. CONCLUSIONS: The UBM measurement method appeared to be most consistent and reproducible when compared to direct measurement techniques. Formalin fixation of the eyes was associated with significantly thinner scleral tissue than with fresh ocular tissue.     

Pharmacokinetics of marbofloxacin in blue and gold macaws (Ara ararauna)

OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. ANIMALS: 10 healthy blue and gold macaws. PROCEDURES: In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. RESULTS: After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microg.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microg/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microg.h/mL, and the harmonic mean terminal half-life was 4.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.     

Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs

OBJECTIVE: To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. ANIMALS: 12 adult mixed-breed and purebred hounds. PROCEDURE: 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. RESULTS: Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.     

The pharmacokinetic behaviour of marbofloxacin in Eurasian buzzards (Buteo buteo) after intraosseous administration

This study reports on the administration of a single dose of marbofloxacin (2 mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO) route, which has been proposed as a rapid and efficient means for the parenteral delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak marbofloxacin concentration (C(max)) in plasma and area under the concentration-time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL, respectively. The time marbofloxacin remained in the plasma after IO administration was relatively short (elimination half-life, t(1/2beta)=4.91+/-0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC value of 85.3h after IO administration. The IO route appears to be practical and effective for the rapid delivery of marbofloxacin to buzzards.     

Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration to ostriches

The pharmacokinetics of marbofloxacin was investigated after intravenous (IV) and intramuscular (IM) administration, both at a dose rate of 5 mg/kg BW, in six clinically healthy domestic ostriches. Plasma concentrations of marbofloxacin was determined by a HPLC/UV method. The high volume of distribution (3.22+/-0.98 L/kg) suggests good tissue penetration. Marbofloxacin presented a high clearance value (2.19+/-0.27 L/kgh), explaining the low AUC values (2.32+/-0.30 microgh/mL and 2.25+/-0.70 microgh/mL, after IV and IM administration, respectively) and a short half life and mean residence time (t(1/2 beta)=1.47+/-0.31 h and 1.96+/-0.35 h; MRT=1.46+/-0.02 h and 2.11+/-0.30 h, IV and IM, respectively). The absorption of marbofloxacin after IM administration was rapid and complete (C(max)=1.13+/-0.29 microg/mL; T(max)=0.36+/-0.071 h; MAT=0.66+/-0.22 h and F (%)=95.03+/-16.89).     

Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A

OBJECTIVE: To determine the long-term toxicity of an intravitreal device releasing continuous cyclosporinee A (CsA) in normal eyes of horses by evaluating clinical signs, electroretinography, and histopathology. Animals Studied Ten adult horses with normal ophthalmic examinations were used in this study Procedure(s) Four horses had one eye implanted with a CsA device, and six horses had the right eye implanted with a CsA-containing device (10 eyes with CsA in total) and the left eye (six eyes in total) with the device without drug (control). The implants were placed in the vitreous of the eyes through a sclerotomy 1 cm posterior to the limbus in the dorso-temporal quadrant of the eye. Scotopic electroretinograms were performed prior to implantation and at 1 week, and at 1, 3, 6, 9, and 12 months postimplantation. Two of the unilaterally implanted horses were euthanized at 1 weeks postimplantation, and two at 6 weeks postimplantation. Two of the bilaterally implanted horses were euthanized at 6 months, two at 9 months, and two at 12 months postimplantation. At euthanasia, the eyes were removed, aqueous and vitreous humor aspirated, and tissues fixed in 10% buffered formalin and processed for histopathology. CsA concentrations were measured by high pressure liquid chromatography in the aqueous and vitreous humors, and in peripheral blood. RESULTS: The devices were tolerated well in 14 of 16 eyes. There was minimal postoperative inflammation in most eyes, with a normal appearance within 7 days. In two eyes implanted with the CsA device, severe inflammation resulted in phthisis bulbi by 28 days. One of these eyes exhibited suspected bacterial endophthalmitis, and one had a sterile endophthalmitis and cataract presumably from trauma to the lens during implantation. In the other 14 eyes, no change was observed in the scotopic electroretinograms (ERG) from preoperative results, and no significant differences between the right (CsA) and left (control device) eyes were observed. CsA levels in the aqueous and vitreous humor, and peripheral blood were below the detection limit of the HPLC. Histologic findings revealed only a mild lymphoplasmacytic cellular infiltrate in the ciliary body and pars plana near the implantation site. CONCLUSIONS: The CsA devices were well tolerated with no long-term complications from the implants themselves. However, complications may occur from inadvertent implantation trauma or contamination during surgery. The long-term safety of the device may make it useful for delivery of CsA in the control of equine recurrent uveitis.     

Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats

The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.     

Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses

OBJECTIVE: To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. ANIMALS: 6 healthy horses. PROCEDURE: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods. RESULTS: Itraconazole reached higher mean +/- SD plasma concentrations after administration of the solution (0.41 +/- 0.13 microg/mL) versus the capsules (0.15 +/- 0.12 microg/mL). Bioavailability after administration of capsules relative to solution was 33.83 +/- 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 +/- 0.94 L/kg) and a long half-life (11.3 +/- 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 +/- 0.17%. CONCLUSIONS AND CLINICAL RELEVANCE: Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses.     

Pharmacokinetics of florfenicol in serum and synovial fluid after regional intravenous perfusion in the distal portion of the hind limb of adult cows

OBJECTIVE: To define the pharmacokinetics of florfenicol in synovial fluid (SYNF) and serum from central venous (CV) and digital venous (DV) blood samples following regional IV perfusion (RIVP) of the distal portion of the hind limb in cows. ANIMALS: 6 healthy adult cows. PROCEDURES: In each cow, IV catheters were placed in the dorsal common digital vein (DCDV) and the plantar vein of the lateral digit, and an indwelling catheter was placed in the metatarsophalangeal joint of the left hind limb. A pneumatic tourniquet was applied to the midmetatarsal region. Florfenicol (2.2 mg/kg) was administered into the DCDV. Samples of DV blood, SYNF, and CV (jugular) blood were collected after 0.25, 0.50, and 0.75 hours, and the tourniquet was removed; additional samples were collected at intervals for 24 hours after infusion. Florfenicol analysis was performed via high-performance liquid chromatography. RESULTS: In DV blood, CV blood, and SYNF, mean +/- SD maximum florfenicol concentration was 714.79 +/- 301.93 microg/mL, 5.90 +/- 1.37 microg/mL, and 39.19 +/- 29.42 microg/mL, respectively; area under the concentration versus time curve was 488.14 +/- 272.53 h*microg*mL(1), 23.10 +/- 6.91 h*microg*mL(1), and 113.82 +/- 54.71 h*microg*mL(1), respectively; and half-life was 4.09 +/- 1.93 hours, 4.77 +/- 0.67 hours, and 3.81 +/- 0.81 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Following RIVP, high florfenicol concentrations were achieved in DV blood and SYNF, whereas the CV blood concentration remained low. In cattle, RIVP of florfenicol may be useful in the treatment of infectious processes involving the distal portion of limbs.     

Ciprofloxacin and ofloxacin aqueous humor concentrations after topical administration in dogs undergoing cataract surgery

OBJECTIVE: To determine if preoperative topical administration of ciprofloxacin or ofloxacin results in aqueous humor drug concentrations that exceed the MIC(90) of common ocular contaminants in dogs undergoing cataract surgery. PROCEDURES: Twelve dogs were treated with topical 0.3% ciprofloxacin and 13 dogs with topical 0.3% ofloxacin once the night before surgery, and then with 1 drop of ciprofloxacin or ofloxacin every 15 min for 2 h immediately before surgery. Aqueous humor samples were taken from each eye immediately before the incision was made and frozen at -70 degrees C. First eye samples (S1) were taken closer to the time of topical treatments than second eye samples (S2). Samples were analyzed by high performance liquid chromatography (HPLC) at the North Carolina State University (NCSU) Clinical Pharmacology laboratory. RESULTS: In ciprofloxacin patients, S1 concentrations were 0.03-0.69 (0.17 median) microg/mL, and S2 concentrations were 0.09-0.95 (0.36 median) microg/mL. Aqueous humor concentrations did not exceed the MIC90 of Streptococcus sp. Few eyes (1/12 OU) exceeded the MIC90 for Staphylococcus sp. or Corynebacterium sp.; moderate numbers (5/12 S1; 8/12 S2) exceeded the MIC90 for E. coli. In ofloxacin patients, S1 concentrations were 0.48-2.81 (1.05 median) microg/mL, and S2 concentrations were 0.45-3.63 (1.30 median) microg/mL. Although few eyes (相似文献   

Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.     

Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of marbofloxacin after subcutaneous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.     

Ascorbic acid levels of aqueous humor of dogs after experimental phacoemulsification

Phacoemulsification has been successfully employed in humans and animals for lens extraction. This ultrasonic extracapsular surgical technique induces hydroxyl radical formation in the anterior chamber, which accumulates despite irrigation and aspiration. In this paper we determined the total antioxidant status of aqueous humor after phacoemulsification by measuring aqueous humor ascorbic acid levels. Mixed-breed dogs (n = 11; weighing about 10 kg) with normal eyes as determined by slit-lamp biomicroscopy, applanation tonometry, and indirect ophthalmoscopy had phacoemulsification performed in one eye with the other eye used as a control. Samples of aqueous humor were obtained by anterior chamber paracentesis before surgery and at days 1, 2, 3, 7, and 15 after surgery. Total aqueous humor antioxidant status was inferred from the capacity of aqueous humor to inhibit free radical generation by 2,2-azobis (2-amidopropane) chlorine. Ascorbic acid concentrations were measured by high-pressure liquid chromatography with UV detection. Protein content was determined with the biuret reagent. Statistical analysis was performed by anova followed by the paired t-test. Total antioxidant capacity was reduced from 48 to 27 min during the first 24 h with a gradual increase thereafter, remaining statistically lower than the control eye until 7 days postoperatively. Reduced levels of ascorbic acid followed this reduction in antioxidant capacity (from 211 to 99 microm after 24 h), remaining lower than the control eye until 15 days postoperatively. Protein concentration in aqueous humor increased from 0.62 mg/mL to 30.8 mg/mL 24 h after surgery, remaining statistically lower than the control eye until 15 days postoperatively. Paracentesis alone did not significantly alter the parameters measured. These results indicate that after phacoemulsification, the aqueous humor ascorbic acid levels and antioxidant defenses in aqueous humor are reduced, indirectly corroborating free radical production in the anterior chamber as a result of phacoemulsification. The inflammatory process consequent to the surgical procedure demonstrated by increased protein content in aqueous humor can also contribute to free radical production and ascorbic acid consumption.     

Evaluation of the ocular penetration of topical alpha-luminol (Galavit®/GVT®)

Purpose Oxidative stress plays a major role in the pathogenesis of many neurodegenerative diseases. It has also been implicated as part of the pathogenic mechanisms in the development of glaucoma. Alpha‐luminol has shown profound anti‐inflammatory and antioxidant effects in both experimental animal and human clinical studies. The purpose of this pilot study was to investigate for the first time the ocular penetration of topical alpha‐luminol. Methods Nine animals were divided into three treated groups (three animals each; one drop OU/n = 18), each group receiving a different concentration of the eyedrop (0.5%, 1.5%, 2.5%). Aqueous humor and peripheral blood samples were obtained from each rabbit at three different timepoints (20 min, 4 h and 12 h). Samples were analyzed by means of high performance liquid chromatography and mass spectrometry; median values were compared. Results Alpha‐luminol was found in the aqueous humor in all treated groups at all timepoints. At the 2nd and 3rd timepoints (4 h and 12 h), aqueous humor levels decreased significantly (P < 0.05) for two of the three dosages tested and it was not detectable in some eyes. The highest aqueous humor concentration of the drug was 272 ng/mL after 20 min (0.0217% of one drop, 2.5% group). Alpha‐luminol was found in the vitreous in two animals, one in the 1.5% and another in the 2.5% group (16.4 and 21.5 ng/mL, respectively), at 12 h. Conclusions Topically administered alpha‐luminol readily penetrates into the anterior chamber and can penetrate into the vitreous chamber. Further investigation is warranted to better understand the intraocular pharmacokinetics of alpha‐luminol.     

Role of bacteria in the pathogenesis of recurrent uveitis in horses from the southeastern United States

OBJECTIVE: To determine the role of intraocular bacteria in the pathogenesis of equine recurrent uveitis (ERU) in horses from the southeastern United States by evaluating affected eyes of horses with ERU for bacterial DNA and intraocular production of antibodies against Leptospira spp. SAMPLE POPULATION: Aqueous humor, vitreous humor, and serum samples of 24 clinically normal horses, 52 horses with ERU, and 17 horses with ocular inflammation not associated with ERU (ie, non-ERU inflammation). PROCEDURES: Ribosomal RNA quantitative PCR (real-time PCR) assay was used to detect bacterial DNA in aqueous humor and vitreous humor from clinically normal horses (n = 12) and horses with chronic (> 3-month) ERU (28). Aqueous humor and serum were also evaluated for anti-Leptospira antibody titers from clinically normal horses (n = 12), horses with non-ERU inflammation (17), and horses with confirmed chronic ERU (24). RESULTS: Bacterial DNA was not detected in aqueous humor or vitreous humor of horses with ERU or clinically normal horses. No significant difference was found in titers of anti-Leptospira antibodies in serum or aqueous humor among these 3 groups. Only 2 horses, 1 horse with ERU and 1 horse with non-ERU inflammation, had definitive intraocular production of antibodies against Leptospira organisms. CONCLUSIONS AND CLINICAL RELEVANCE: In horses from the southeastern United States, Leptospira organisms may have helped initiate ERU in some, but the continued presence of the organisms did not play a direct role in the pathogenesis of this recurrent disease.     

Occurrence of various immunoglobulin isotopes in horses with equine recurrent uveitis (ERU)

We investigated 30 healthy eyes and 41 eyes with ERU from 57 horses. The total immunoglobulin titers and titers of IgGa, IgGb, IgM were measured in aqueous humour, vitreous and serum using different ELISA techniques. Every sample investigated contained detectable amounts of immunoglobulins. Compared to control eyes significantly increased titers were found in the aqueous humour and vitreous of the ERU eyes for all immunoglobulin isotypes studied (p < or = 0.01). While IgM was detected in only 2 out of thirty aqueous humour and in none of the thirty vitreous samples of healthy eyes, 79.6% of samples of ERU eyes revealed considerable IgM titers. Changes of the IgGa/IgGb ratio in the eye as compared to that in the autologous serum was more frequent in affected than in healthy eyes. In contrast to the intraocular immunoglobulins there were no significant differences in immunoglobulin serum titers in healthy horses and those affected with ERU (p > 0.05). In conclusion, the results argue for a physiological appearance of immunoglobulins in the healthy eye. The increased titers of immunoglobulins in eyes stricken with ERU might be signs either of a local ocular production of antibodies and/or an increased permeability of intraocular barriers.     

Disposition kinetics and pharmacokinetics--pharmacodynamic integration of difloxacin against Staphylococcus aureus isolates from rabbits

The pharmacokinetics of difloxacin were studied following intravenous (IV), subcutaneous (SC) and oral administration of 5mg/kg to healthy white New Zealand rabbits (n = 6). Difloxacin concentrations were determined by HPLC assay with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of difloxacin against different strains of S. aureus from different european countries was performed in order to compute the main pharmacodynamic surrogate markers. The plasma difloxacin clearance (Cl) for the IV route was (mean +/- SD) 0.41 +/- 0.05 L/h kg. The steady-state volume of distribution (V(ss)) was 1.95 +/- 0.17 L/kg. The terminal half-life [Formula: see text] was (mean+/-SD) 4.19+/-0.34 h, 7.53 +/- 1.32 h and 8.00 +/- 0.45 h after IV, IM and oral, respectively. From this data, it seems that a 5 mg/kg dose difloxacin would be effective by SC and oral routes in rabbits against bacterial isolates with MIC0.1 microg/mL.