Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs

Objectives

Determine tear film kinetics with different fluorescein concentrations and repeated eye drop administration at various time intervals.

Animals Studied

Six healthy Beagles.

Procedures

Six experiments were conducted on separate days: single eye drop administration (control) or two separate eye drops administered at 30 s, 1, 2, 5, and 10 min intervals. For each experiment, one eye received 0.3% fluorescein solution while the other eye received 1% fluorescein solution, and tear fluid was collected with capillary tubes at 0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, and 180 min. Fluorescein concentrations were measured using automated fluorophotometry.

Results

Compared with 0.3% solution, eyes receiving 1% fluorescein solution had significantly higher tear film concentrations (p ≤ .046) and the area-under-the-fluorescein-time curve was twofold greater (p = .005). Compared with control: (i) Tear film concentrations were significantly higher for up to 20 min when repeating administration 30 s to 5 min after the first drop (p ≤ .006); (ii) The highest increase in area-under-the-curve was obtained with 2 and 5 min intervals for 0.3% (+109%–130%) and 1% solutions (+153%–157%); (iii) The highest increase in median precorneal retention time (defined as tear film concentration < 5% from baseline values) was obtained with 5 min intervals for 0.3% (55 min vs. 15 min in control) and 2–5 min intervals for 1% solutions (50 min vs. 25 min in control).

Conclusions

Drug delivery to the ocular surface can be enhanced by using more concentrated formulations and/or by repeating eye drop administration 2–5 min after the first dose.     

A dose‐finding study with a novel water‐soluble formulation of paclitaxel for the treatment of malignant high‐grade solid tumours in dogs

A new formulation of water‐soluble paclitaxel (Paccal® Vet) has been developed for canine cancer patients, without the need for pre‐medication (traditionally required in non‐water‐soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression‐free and overall survival and to evaluate single‐dose pharmacokinetics in tumour‐bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150 mg m^–2 intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression‐free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water‐soluble formulation of paclitaxel suggesting successful administration and being safely used without pre‐medication in dogs.     

Misconceptions surrounding the relationship between journal impact factor and citation distribution in veterinary medicine

Objective

To define the relationship between journal impact factor (JIF) and citation distribution in veterinary journals. Citation distribution is a summary of the number of citations of individual papers published in a defined period, and JIF is said to represent the mean number of citations received by a paper published in a given journal. JIF is criticized for promoting unimportant differences between journals, exaggerating small differences in journal citation distributions by misrepresenting a skewed citation distribution. The hypothesis was that veterinary journals have a skewed citation distribution and that median citation rates between journals would be smaller than that indicated by JIF.

Comparison of three rebound tonometers in normal and glaucomatous dogs

Objective

The objectives of the study were to compare intraocular pressure (IOP) readings across a wide range and obtained via three rebound tonometers in ADAMTS10-mutant Beagle-derived dogs with different stages of open-angle glaucoma (OAG) and normal control dogs and to investigate the effect of central corneal thickness (CCT).

Animals Studied

Measurements were performed on 99 eyes from 50 Beagle-derived dogs with variable genetics—16 non-glaucomatous and 34 with ADAMTS10-OAG. Seventeen OAG eyes were measured twice—with and without the use of IOP-lowering medications.

Procedures

IOP was measured in each eye using three tonometers with their “dog” setting—ICare® Tonovet (TV), ICare® Tonovet Plus® (TVP), and the novel Reichert® Tono-Vera® Vet (TVA)—in randomized order. CCT was measured with the Accutome® PachPen. Statistical analyses included one-way ANOVA, Tukey pairwise comparisons, and regression analyses of tonometer readings and pairwise IOP-CCT Pearson correlations (MiniTab®).

Results

A total of 116 IOP measurements were taken with each of the three tonometers. When comparing readings over a range of ~7–77 mmHg, mean IOPs from the TV were significantly lower compared with TVP (−4.6 mmHg, p < .001) and TVA (−3.7 mmHg, p = .001). We found no significant differences between TVA and TVP measurements (p = .695). There was a moderate positive correlation between CCT and IOP for TVA (r = 0.53, p < .001), TVP (r = 0.48, p < .001), and TV (r = 0.47, p < .001).

Conclusions

Our data demonstrate strong agreement between TVP and TVA, suggesting that the TVA may similarly reflect true IOP values in canines. CCT influenced IOP measurements of all three tonometers.     

An eye on the Shih Tzu dog: Ophthalmic examination findings and ocular surface diagnostics

Objective

To characterize the ocular surface parameters and determine the prevalence of ocular pathology in Shih Tzu dogs.

Animal Studied

Fifty Shih Tzu dogs (28 male, 22 female).

Procedures

Each dog underwent a complete ophthalmic examination (recording any pathology) and a series of diagnostics, allowing for a 10 min-interval between tests: intraocular pressure (IOP), blink rate, palpebral fissure length (PFL), corneal tactile sensation (CTS), Schirmer tear test and nasolacrimal reflex without (STT-1, NL-STT1) and with topical anesthesia (STT-2, NL-STT2), tear ferning, strip meniscometry test (SMT), tear film breakup time (TFBUT), and punctate fluorescein staining (PFS) of the cornea.

Results

Mean ± SD test values were as follows: IOP (17.9 ± 3.7 mmHg), blink rate (2.4 ± 1.4 blinks/min), PFL (23.8 ± 1.8 mm), CTS (1.8 ± 0.7 cm), STT-1 (22.0 ± 5.5 mm/min), NL-STT1 (24.2 ± 4.7 mm/min), STT-2 (16.9 ± 6.5 mm/min), NL-STT2 (18.5 ± 7.5 mm/min), SMT (7.5 ± 3.5 mm/5 s), TFBUT (5.3 ± 2.4 s), tear ferning (1.3 ± 0.7), and PFS (1.6 ± 0.6). PFL was significantly greater in male vs. female Shih Tzus (p< .001). Age was negatively correlated with TFBUT results (r = −0.31, p = .027). Lagophthalmos was observed in 82% eyes. Ocular surface pathology was common, including adnexal abnormalities (100% eyes with caruncular trichiasis and medial lower lid entropion) and corneal opacification (27% pigmentation, 20% fibrosis, 12% neovascularization).

Conclusions

Qualitative tear film deficiency (low TFBUT), along with several anatomical abnormalities that promote ocular irritation and reduce globe protection, together help explain the concerningly high prevalence of ocular surface disease in the Shih Tzu breed. Prophylactic measures (e.g., medial canthoplasty, topical lubrication) could be considered to improve ocular health in Shih Tzus.     

Comparison of the TONOVET Plus®, TonoVet®, and Tono-Pen Vet™ tonometers in normal cats and cats with glaucoma

Objectives

To determine the accuracy, precision, and clinical applicability of the ICare® TONOVET Plus (TVP) in cats.

Animals and Procedures

IOP readings obtained with the TVP were compared to values obtained concurrently with the original TONOVET (TV01) and Tono-Pen Vet™ (TP) in 12 normal cats (24 eyes) and 8 glaucomatous LTBP2-mutant cats (13 eyes) in vivo. Reproducibility of TVP readings was also assessed for three observers in the above cats. The anterior chambers of five different normal cat eyes were cannulated ex vivo. IOP was measured with the TVP, TV01, and TP at manometric IOPs ranging from 5 to 70 mmHg. Data were analyzed by linear regression, ANOVA and Bland–Altman plots. ANOVA was used to assess reproducibility of TVP readings obtained by different observers and an ANCOVA model controlled for variation of individual cats. p < .05 was considered significant.

Results

TVP values strongly correlated with TV01 values (y = 1.045x + 1.443, R² = .9667). The TP significantly underestimated IOP relative to the TVP and TV01, particularly at high IOP. IOP values obtained by 1 observer were significantly higher (~1 mmHg average) compared to the other 2 observers via ANCOVA analysis (p = .0006479 and p = .0203). Relative to manometry, the TVP and TV01 were significantly more accurate (p < .0001) and precise (p < .0070) than the TP in ex vivo eyes.

Conclusions

IOP readings obtained with the TVP and TV01 are broadly interchangeable between models and between observers, but subtle differences may be important in a research context. TP readings vastly underestimate high IOP in feline glaucoma.     

Anterior segment fluorescein angiography of the normal feline eye using a dSLR camera adaptor

Purpose To describe anterior segment fluorescein angiography (ASFA) of the normal feline eye using a digital single‐lens reflex (dSLR) camera adaptor. Animals Ten cats free of ocular and systemic disease were evaluated. Methods All cats received maropitant citrate (1.0 mg/kg SQ) and diphenhydramine (2.0 mg/kg SQ) 20 min prior to anesthesia using propofol (4 mg/kg IV bolus, 0.2 mg/kg/min CRI). Standard color and red‐free images were obtained prior to the administration of 10% sodium fluorescein (20 mg/kg IV). Imaging was performed using a dSLR camera (Canon 7D), dSLR camera adaptor, camera lens (Canon EF‐S 60 mm f/2.8 macro), and an accessory flash (Canon 580EXII). Imaging occurred at a rate of 1/second immediately following IV bolus of sodium fluorescein for a total of 30 s, then at 1, 2, 3, 4, 5, and 10 min. Results Ten cats with an average age of 3.7 ± 0.9 years and various iris colors were imaged. Arterial, capillary, and venous phases occurred 4.6, 7.8, and 8.9 s postinjection, respectively. Visibility of the vasculature was not impaired by the degree of iris pigmentation. Patency of a persistent pupillary membrane was noted in one cat. Vessel leakage was common, as well as, leakage into the aqueous humor. Proper patient positioning and restricted ocular movements were critical. No adverse events were noted. Conclusions This study demonstrates ASFA findings in normal feline eyes using a cost‐effective dSLR camera adaptor. Fluorescein leakage from vessels and into the aqueous humor was a common finding. Visibility of iris vasculature was not impaired by the degree of iris pigmentation.     

Survey of ocular abnormalities in draft horses

Objective

To determine the prevalence of ocular disease in draft horses in the United States.

Animals

Draft horses of various breeds and ages.

Procedure

Nondilated ophthalmic examination was performed using slit lamp biomicroscopy and indirect ophthalmoscopy. Intraocular pressures were measured when possible.

Results

One hundred sixty-five draft horses were examined. Age range: 10 days to 33 years (mean 10.8 years, median 10 years); 87 geldings (52.7%), 71 mares (43.0%), 7 stallions (4.2%); 64 Percherons (38.8%), 51 Belgians (30.9%), 29 Clydesdales (17.6%), 15 Shires (9%), and 6 other draft breed (3.6%). Intraocular pressure: mean 24.7 mmHg OD, range 13-37 mmHg; mean 25.0 mmHg OS, range 11-37 mmHg. Vision-threatening disease was present in 9 horses (5.5%): complete cataracts 1, post-traumatic optic nerve atrophy 1, uveitis and secondary glaucoma 1, retinal detachment 1, large chorioretinal scar 3, phthisis bulbi 2. Non-vision-threatening ocular disease was present in 56 horses (33.9%) involving one or more ocular structures: eyelid trauma/notch defect 14 (8.5%), SCC-type adnexal lesions 12 (7.3%), corneal scars 16 (9.7%), keratitis 6 (3.6%), corpora nigra cyst 15 (9.1%), incipient/punctate cataract 50 (30.3%), vitreous degeneration 10 (6.1%), asteroid hyalosis 1, “bullethole” chorioretinal scars 3, RPE coloboma 1. Linear keratopathy was present in 28 horses (17%) with 2/28 having concurrent vision threatening ocular disease.

Conclusions

Ocular abnormalities, in particular minor cataracts, were relatively common in this population, but not typically vision-threatening. Additionally, this survey demonstrated a greater prevalence of linear keratopathy in draft horses compared with reports in other breeds; however, it does not appear to be associated with concurrent ocular disease.     

The effects of moxifloxacin ophthalmic solution 0.5% or gatifloxacin ophthalmic solution 0.3% treatment on corneal wound healing in pigmented rabbits following anterior keratectomy

Purpose These studies examined corneal healing rates, Type‐IV collagen and zonula occludens membrane‐associated protein (ZO‐1) expression, as well as aqueous PGE₂ and IL‐1β concentrations in pigmented rabbits treated with either moxifloxacin 0.5%, gatifloxacin 0.3% or BSS^® following anterior keratectomy. Methods Anterior keratectomy surgery was followed by topical administration with commercial ophthalmic formulations of either moxifloxacin or gatifloxacin or BSS^® (TID for 96 h). Images of the fluorescein‐stained healing corneas were analyzed for wound area. At 48 or 96 h following surgery, aqueous humor samples were collected and analyzed for the inflammatory mediators PGE₂ and IL‐1β using an ELISA. The corneas were subsequently evaluated using both scanning and transmission electron microscopy. In a second parallel study, corneas were evaluated at both 48 and 96 h for Type‐IV collagen and ZO‐1 expression using immunohistochemistry. Results Fluorescein‐stained corneal images at 96 h postsurgery demonstrated that 90% ± 8% re‐epithelialization for moxifloxacin, 81% ± 14% for gatifloxacin, and 88 ± 6% for BSS^® (P > 0.05). PGE₂ levels in the aqueous humor of fluoroquinolone treated eyes were reduced at 48 h compared to BSS^® treated eyes. IL‐1β was undetectable in all samples. No differences in Type‐IV collagen or ZO‐1 expression were observed between any treatment groups. There were no differences between groups in histological appearance or in ultrastructural healing processes. Conclusions These studies demonstrated that the commercial ophthalmic formulations of moxifloxacin and gatifloxacin were similar to each other in their effects on the levels of aqueous humor PGE₂ and rates of corneal wound re‐epithelialization.     

Effects of Final Implant Type and Supplementation of Melengestrol Acetate® on Finishing Feedlot Heifer Performance,Carcass Characteristics,and Feeding Economics

Three finishing experiments were conducted in commercial feedlots to determine effects of implant programs on finishing heifer performance, carcass characteristics, and economics. A total of 3,307 heifers were used in the three experiments. Overall, four treatment comparisons were tested within the three separate experiments. Treatment groups included the following: 1) heifers implanted with Synovex® Plus (Fort Dodge Animal Health; Fort Dodge, IA) but not fed melengestrol acetate (MGA®; Pharmacia and Upjohn Company; Kalamazoo, MI), 2) heifers implanted with Synovex® Plus and fed MGA®, 3) heifer implanted with Revalor®-H (Intervet Inc.; Millsboro, DE) and fed MGA®, and 4) heifers implanted with Finaplix®-H (Intervet Inc.) and fed MGA®. Common treatments of Synovex® Plus and dietary MGA® as well as Finaplix®-H and dietary MGA® were used in each of the three experiments. Finishing heifers fed MGA® and implanted with Synovex® Plus had 3.9 and 4.1% greater (P<0.10) ADG than did heifers implanted with Revalor®-H or Finaplix®-H and fed MGA®, respectively. Daily gain did not differ for heifers implanted with Revalor®-H or Finaplix®-H. Feeding MGA® to heifers implanted with Synovex® Plus increased ADG and decreased deleterious effects on quality grade; however; carcasses had greater fat thickness. Fewer carcasses of heifers fed MGA® and implanted with Synovex® Plus or Revalor®-H were graded Choice in comparison with the carcasses of those implanted with Finaplix®-H. When selling heifers on a carcass-merit basis, net returns did not differ among heifers implanted with Synovex® Plus, Revalor®-H, or Finaplix®-H when fed MGA®. When selling heifers on a dressed basis, net return was maximized (P<0.10) with the use of Synovex® Plus and supplementation with MGA® compared with Synovex® Plus and no MGA® supplementation, Revalor®-H and MGA® supplementation, and Finaplix®-H and MGA® supplementation.     

Ophthalmic examination findings in adult pygmy goats (Capra hicus)

Objective To document normal ophthalmic findings and ocular abnormalities in captive adult pygmy goats. Animals studied Ten healthy adult pygmy goats (five male, five female; 5–11 years of age; 26–45 kg body mass) underwent complete ophthalmic examinations. Procedure Direct illumination, diffuse and slit‐beam biomicroscopy, indirect ophthalmoscopy, IOP measurements and Schirmer tear tests were performed. TonoVet^® rebound tonometry, followed by topical application of 0.5% ophthalmic proparacaine, and Tono‐Pen XL^® applanation tonometry were performed in each eye to obtain estimates of IOP. Results Ophthalmic abnormalities included corneal scars and pigmentation, incipient cataracts, lenticular sclerosis, and vitreal veiling. Mean STT values were 15.8 mm/min, with a range of 10–30 mm/min. Mean IOP values were 11.8 mmHg for TonoVet^®‐D, with a range of 9–14 mmHg; 7.9 mmHg for TonoVet^®‐P, with a range of 6–12 mmHg; and 10.8 mmHg for Tono‐Pen XL^®, with a range of 8–14 mmHg. Conclusions Ophthalmic examination findings in adult pygmy goats, including normal means and ranges for STT and IOP measurements, using applanation and rebound tonometry, are provided.     

A remote fluorescein staining and photography protocol for monitoring of ulcerative keratitis in small animal patients: A pilot study

Objective

To describe a protocol for corneal ulcer monitoring utilizing daily fluorescein staining and evaluation of owner-acquired anterior segment images.

Animal studied

Nine client-owned small animal patients (eight dogs, one cat) diagnosed with superficial corneal ulcers at the University of Georgia Veterinary Capitalize Hospital.

Procedure(s)

In addition to routine ulcer therapy, patients were discharged with supplies to perform daily fluorescein staining including a Quikvue® cobalt blue light camera adapter. Fluorescein staining was performed daily, photographs and/or videos were acquired at home by the patient's owner(s), and images were analyzed daily by trained personnel. In-house examinations were performed weekly and within 24 h after the ulcer had appeared healed on photographs.

Results

All (9/9) owners were able to take interpretable photographs. The majority (6/9) of patients had images successfully detailing their ulcer healing progress. One (1/9) patient appeared healed on images, but on subsequent examination had persistent ulceration covered by third eyelid elevation. Two (2/9) patients had persistent ulceration, consistent on both images and examination, but exited the study prematurely prior to ulcer healing.

Conclusions

Remote fluorescein staining and image evaluation can be considered as an adjunct for monitoring ulcer healing but should not be used alone or as a substitute for ophthalmic examinations. Ulcers under the third eyelid have potential to be missed on image evaluation alone.     

Changes in endotracheal tube intracuff pressure and air leak pressure over time in anesthetized Beagle dogs

Objective

To evaluate endotracheal tube intracuff pressure (P_cuff) changes over time and the effect of these changes on air leak pressure (P_leak).

Evaluation of the in vivo behaviour of gentamicin sulphate ocular mini-tablets in ponies

The in vivo behaviour of 5% gentamicin sulphate ocular mini-tablets (2-mm diameter, 6.525 mg weight) was compared with gentamicin eye drops in six ponies. Two mini-tablets were inserted on the bulbar conjunctiva of the right eye while a similar dose of gentamicin was administered via eye drops in the left eye. Irritation induced by the mini-tablets and the eye drops was evaluated using a visual analogue scale (0-10). Tears were sampled with ophthalmologic absorption triangles for 1 min for the determination of the concentration of gentamicin sulphate using a microbiological plate diffusion method. Irritation induced by the tablets was minor and clinically acceptable (overall median score of 1.7 +/- 1.4). Eye drops induced a sharp increase in gentamicin sulphate concentration (364.4 microg/mL after 5 min) followed by a fast decline (10.8 microg/mL after 60 min). The increase in concentration induced by the ocular mini-tablets was less pronounced (up to 56.2 microg/mL after 30 min) and followed by a gradual decrease; the concentration remained above 15 microg/mL for 8 h. Ocular 5% gentamicin sulphate mini-tablets are clinically well-tolerated in ponies, assuring a constant concentration in the tears for at least 8 h.     

Comparison of a rebound and an applanation tonometer for measuring intraocular pressure in normal rabbits

Objective To compare intraocular pressure (IOP) measurements made on healthy adult rabbits without the effect of tranquilizers using the new applanation tonometer, Tono‐Pen Avia^®, and the rebound tonometer Tonovet^®. Methods Intraocular pressure was measured throughout the day (6:00, 9:00, 12:00, 15:00, and 18:00 h) in 38 adult New Zealand White rabbits (76 eyes). The animals were 20 males and 18 females, with a mean weight of 3.5 kg and an average age of 6 months. A complete ocular exam (including Schirmer tear test, fluorescein staining, slit‐lamp biomicroscopy, and direct ophthalmoscopy) was performed on all animals at the beginning of the trial. Rebound tonometry was performed, and after 10 min, anesthetic drops were instilled and applanation tonometry was carried out. IOP values obtained using the two techniques were analyzed statistically. Results The mean IOP was 9.51 ± 2.62 mmHg with Tonovet^®, and 15.44 ± 2.16 mmHg with the Tono‐Pen Avia^®. Significant differences between measurements with the two tonometers were observed (P < 0.001). The linear regression equation describing the relationship between the two tonometers was y = 0.4923x + 10.754 (y = Tonovet^® and x = Tono‐Pen Avia^®). High IOPs were recorded in the early measurements (6:00), but the average IOPs from both devices were statistically similar throughout the day (P = 0.086). The correlation coefficient was r² = 0.357. No significant difference in IOP regarding gender was observed. Conclusion The Tono‐Pen Avia^® recorded higher levels of IOP compared with the Tonovet^®. Early in the day, the IOP of rabbits was higher than later in the day, regardless of the tonometer used.     

Comparative in vitro efficacy of antimicrobial shampoos: a pilot study

This study compared the antimicrobial efficacy of shampoos against meticillin‐sensitive Staphylococcus pseudintermedius (MSSP), meticillin‐resistant S. pseudintermedius (MRSP), antibiotic‐sensitive Pseudomonas aeruginosa (PA), multidrug‐resistant P. aeruginosa (MDR‐PA) and Malassezia pachydermatis. Three isolates were incubated for 10, 30 and 60 min with each shampoo diluted in phosphate‐buffered saline. Aliquots were then incubated for 16–18 h on sheep blood agar (bacteria) or for 3 days on Sabouraud’s dextrose agar (Malassezia). The minimal bactericidal concentrations (MBCs) for chlorhexidine products (Malaseb^®, Pyoderm^®/Microbex^® and Hibiscrub^®) were 1:1,024–1:2,048 for MSSP and MRSP, 1:512–1:1,024 for PA and MDR‐PA, and 1:2,048–1:5,096 for Malassezia at all time points. The MBCs for benzoyl peroxide (Paxcutol^®) for MSSP and MRSP were 1:2–1:8 at 10 min, and 1:256 after 30 and 60 min. A 1:2 dilution was effective against Pseudomonas, and 1:512–1:1,024 dilutions were effective against Malassezia at all time points. The MBCs for ethyl lactate (Etiderm^®) for MSSP and MRSP were 1:2 at 10 min, and 1:2–1:16 after 30 and 60 min. A 1:2 dilution was effective against Pseudomonas, and a 1:512 dilution was effective against Malassezia at all time points. Chloroxylenol (Coatex^®) and acetic acid–boric acid (Malacetic^®) were not effective against MSSP, MRSP or Pseudomonas. Both were effective against Malassezia at 1:8–1:16 dilution at 10 min, and at 1:8–1:32 dilution after 30 and 60 min. In conclusion, chlorhexidine appeared to be the most effective topical biocide, and MRSP and MDR‐PA were no less susceptible than antibiotic‐sensitive organisms. These results should, however, be confirmed with larger numbers of isolates.     

Pharmacokinetics of intrarectal omeprazole in alpacas

Marmulak, T., Stanley, S., Kass, P.H., Wiebe, V., McKemie, D., Pusterla, N. Pharmacokinetics of intrarectal omeprazole in alpacas. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.00149.x. The purpose of this study was to evaluate the pharmacokinetics of omeprazole in three different vehicles when administered rectally to six alpacas. Alpacas were given single doses of omeprazole (4 mg/kg) in a double‐blinded, randomized cross‐over design with a 1 week washout period. Omeprazole formulations consisted of (1) Treatment A: omeprazole paste mixed in surgical lubricant (2) Treatment B: omeprazole capsule contents in 8.4% sodium bicarbonate and (3) Treatment C: omeprazole capsule contents in surgical lubricant and 8.4% sodium bicarbonate solution. Plasma samples were drawn at 0, 5, 10, 15, 30, 45, 60, 90, 120, 180, 300 and 480 min. Omeprazole plasma concentrations were determined by high‐pressure liquid chromatography‐mass spectrometry. Pharmacokinetic results demonstrated median peak plasma concentrations (C_max) of 7.35 (3.2–15.2), 7.30 (1.7–10.9) and 8.65 (1.8–19.3) ng/mL and median area under the concentration curve (AUC_(0–180)) of 747 (237–1681) min·ng/mL, 552.9 (39–1063) min·ng/mL, and 972 (107–1841) min·ng/mL for treatments A, B and C, respectively. The median half‐lives were similar between groups: 38, 50, and 53 min. As a result of the low measured omeprazole plasma concentrations, it is assumed that rectal absorption of omeprazole is poor in alpacas and not an effective route of administration.     

Determination of tear break-up time reference values and ocular tolerance of tetracaine hydrochloride eyedops in healthy horses

Reasons for performing study: Tetracaine hydrochloride (THCl) has been reported to cause irritation in dogs. In man, some topical anaesthetics have been shown to disrupt the tear film. Tear break‐up time (TBUT) is a useful test allowing an assessment of the quality of the precorneal tear film. Only one TBUT value has been reported in horses with no information on the technique used. Objectives: To provide a method for performing the TBUT in horses and to report any side effects of a single application of THCl in clinically normal horses, particularly on the stability of the tear film. Methods: In Study 1, one drop of 0.5 or 1% THCl was applied to one eye of 20 horses divided in 2 groups. Treated eyes were assessed for the development of side effects 2.5 and 5 min after treatment. In Study 2, the TBUT was measured in both eyes of 2 groups of 10 horses, before and 2.5 and 5 min after, instillation of one drop of either 0.5 or 1% THCl. Results: No animals developed any ocular side effect after instillation. Basal TBUT was 8.3 ± 1.3 s. TBUT decreased from baseline 5 and 2.5 min after application of one drop of 0.5% THCl and one drop of 1% THCl, respectively. Conclusions: A technique to measure the TBUT in healthy horses is described and normal range values that could be used as a reference were obtained. Potential relevance: THCl is well tolerated in horses but lowers the TBUT.     

A comparison of the bioequivalence of 0.5% fenbendazole top dress pellets or 10% fenbendazole oral suspension against a spectrum of equine parasites.

A controlled test was conducted to assess the efficacy bioequivalence of a single dose of 0.5% fenbendazole (FBZ) top dress pellets to a 10% FBZ suspension formulation (Panacur suspension 10%, Hoechst Roussel Vet). Thirty horses with naturally-acquired parasite infections, in replicates of three, were used. Strongyle egg per gram counts were not significantly different (P>0.1) between groups pretreatment, but FBZ treated groups were significantly different from the control group post-treatment. At necropsy, which occurred seven to nine days post-treatment, two methods of nematode recovery were compared to assess whether a small aliquot can be used in a control test to determine efficacy against large as well as small strongyles. Both post mortem worm recovery techniques revealed similar efficacies of both formulations (>95%) against small and large strongyles, but large differences in the number of worms recovered. Six species of small strongyles comprised 96% of all the small strongyles recovered: Coronocyclus coronatus, Cylicocyclus insigne, Cylicostephanus longibursatus, Cylicocyclus brevicapsulatus, Cylicocyclus nassatus, and Cyathostomum catinatum. The results of this study demonstrated therapeutic bioequivalence between FBZ formulations and also the need to sample at least a 10% aliquot to accurately estimate number of large strongyles. No adverse reactions to treatment were detected.