Skip to main content
NCBI home page
Wiley Open Access Collection logoLink to Wiley Open Access Collection
. 2026 Mar 24;49(4):378–384. doi: 10.1111/jvp.70069

Ocular Pharmacokinetics of Topical Chloramphenicol in Dogs: Effects of Concentration and Vehicle Formulation

Bar Fruchter 1, Oren Pe'er 1, Shir Gonen 1, Lionel Sebbag 1,✉
PMCID: PMC13371850  PMID: 41877401

ABSTRACT

This study compared tear film exposure and retention of four chloramphenicol ophthalmic formulations in dogs, evaluating the effects of drug concentration (0.2% to 5%) and vehicle type (solution vs. ointment). Eight healthy dogs were enrolled in a randomized paired‐eye crossover study consisting of two sessions with a 7‐day washout. Tear samples were collected via microcapillary tubes at intervals up to 480 min post‐instillation, and concentrations were quantified using UV–Vis spectrophotometry. Results showed that chloramphenicol exposure was significantly enhanced by higher concentrations and ointment vehicles. The 0.8% solution achieved a 2.2‐fold increase in AUC0–480 over the 0.2% solution, while the 5% ointment provided a 3.0‐fold increase over the 1% ointment. Tear concentration at 480 min was superior for ointments, with the 5% formulation maintaining 88.7 ± 6.8 μg/mL, whereas both solutions fell below quantification limits by the end of the interval. Overall exposure did not differ significantly between the 0.8% solution and 1% ointment. In conclusion, chloramphenicol exposure on the ocular surface depends on both concentration and formulation. High‐concentration ointments maximize exposure and prolong retention, providing a pharmacokinetic framework for optimizing therapy in canine bacterial keratitis.

Keywords: antibiotic therapy, bacterial keratitis, ocular drug delivery, ophthalmic ointment, ophthalmic solution, pharmacokinetics

1. Introduction

Bacterial keratitis is a vision‐ and globe‐threatening disease in dogs characterized by corneal epithelial disruption and colonization by opportunistic pathogens, primarily Staphylococcus pseudintermedius , Streptococcus species, and Pseudomonas aeruginosa (Tolar et al. 2006; Hewitt et al. 2020; Casemiro et al. 2025). Prompt antimicrobial therapy is essential to prevent complications such as keratomalacia or perforation (Ollivier 2003). Chloramphenicol is a bacteriostatic antibiotic widely used in clinical patients due to its broad‐spectrum activity and favorable physicochemical properties, including low molecular weight and lipophilicity, which facilitate effective penetration through the corneal epithelium (Robert and Adenis 2001). Recent surveillance data confirm its efficacy against common canine isolates: Hewitt et al. (2020) and Hindley et al. (2016) reported 83% and 67% susceptibility across all isolates, respectively (Hewitt et al. 2020; Hindley et al. 2016), Tsvetanova et al. (2021) reported 60%–88% susceptibility for β‐haemolytic Streptococcus and coagulase‐positive Staphylococcus (Tsvetanova et al. 2021), while Casemiro et al. (2025) reported over 80% susceptibility for Staphylococcus and Enterobacteriaceae family (Casemiro et al. 2025). A similar trend in chloramphenicol efficacy has also been reported in humans with ocular bacterial infections (Robert and Adenis 2001; Bale et al. 2023).

Topical ophthalmic solution (eye drop) is the standard for ocular drug delivery, but the effectiveness of aqueous solutions is limited by rapid precorneal elimination via reflex blinking and nasolacrimal drainage (Davies 2000; Sebbag, Allbaugh, et al. 2019; Sebbag and Mochel 2020). In dogs, the basal tear turnover rate is 12.2% per minute while the reflex tear turnover rate is 50% per minute (Sebbag, Allbaugh, et al. 2019); as such, canine studies show that tear film concentrations can decrease by 20%–45% within the first minute and by 80%–95% within 15 min after eye drop administration (Sebbag, Allbaugh, et al. 2019; Sebbag, Kirner, et al. 2020). To mitigate this rapid clearance, ophthalmic ointments are formulated to increase viscosity, which prolongs contact with the ocular surface, reduces drainage, and potentially enhances therapeutic efficacy through sustained drug release (Hardberger et al. 1975; Bedos et al. 2023).

Previous studies in humans and rabbits have demonstrated that ointments achieve significantly longer residence times compared to solutions (Hardberger et al. 1975; Greaves et al. 1993; Hyndiuk et al. 1988). However, direct extrapolation of these findings to dogs is not possible because of species‐specific differences in the ocular surface physiology and tear film dynamics (Sebbag and Mochel 2020). A recent study in dogs confirmed that a petrolatum‐based ointment has a precorneal retention time of 40 min, significantly longer than the 10 min observed for artificial tear solution (Bedos et al. 2023). Despite these findings, the interplay between chloramphenicol concentration and vehicle formulation has not been directly compared in the canine eye.

The objectives of this study were to evaluate chloramphenicol levels in canine tears following the topical administration of four specific formulations: 0.2% and 0.8% ophthalmic solutions, and 1% and 5% ophthalmic ointments. We hypothesized that the pharmacokinetics of chloramphenicol would vary among formulations, with the high‐concentration ointment exhibiting superior retention in the tear film and greater overall drug exposure. Such data are critical for optimizing dosing and guiding clinical decision‐making in dogs with bacterial keratitis.

2. Material and Methods

2.1. Dogs

Eight healthy Labrador Retrievers (4 males, 4 females; 16 eyes) were recruited from the Israeli Guide Dog Center for the Blind. Dogs were aged 1.6 ± 0.1 years and weighed 31.8 ± 3.9 kg. Prior to study inclusion, all dogs were confirmed to be ophthalmoscopically healthy based on a complete physical and ophthalmic examination performed by a board‐certified veterinary ophthalmologist (LS), including slit‐lamp biomicroscopy (SL‐17; Kowa Company), rebound tonometry (TonoVet Plus; Icare Finland), and indirect ophthalmoscopy (Keeler Vantage; Keeler Instruments). Dogs were excluded if they had any evidence of ocular surface disease, known drug sensitivities, or systemic illness. The dogs were group‐housed in a climate‐controlled environment with a 12‐h light/dark cycle. The study was approved by the Institutional Animal Care and Use Committee of Israel's Ministry of Health (permit NPC‐VH‐IL‐2510‐415‐2).

2.2. Experimental Design

The study utilized a randomized, crossover design consisting of two separate experimental sessions separated by a 7‐day washout period. In the first session, dogs received two chloramphenicol ophthalmic solutions (one in each eye): 0.2% chloramphenicol combined with polymyxin B (Phenimixin, Vitamed Pharmaceutical Industries Ltd. Binyamina, Israel) and 0.8% chloramphenicol (Crotax, VAPP, Carnaxide, Portugal). In the second session, dogs received two chloramphenicol ophthalmic ointments (one in each eye): 5% chloramphenicol (Synthomycine, Rekah Pharmaceutical Ltd., Holon, Israel) and 1% chloramphenicol (Crotax, VAPP, Carnaxide, Portugal). In each session, treatment allocation to the left or right eye was randomized (“coin toss”).

2.3. Drop Size and Ointment Amount

To standardize the volume of administration, a preliminary evaluation of drop size was performed. A single drop of each ophthalmic solution was dispensed individually into a microcentrifuge tube, and the volume was measured using a calibrated pipette (10–100 μL, P100, Gilson, France). This process was repeated 100 times per formulation. The mean ± standard deviation drop volume was 41.1 ± 2.5 μL for the 0.8% solution and 41.6 ± 1.6 μL for the 0.2% solution. Consequently, a standardized volume of 41 μL was used for all solution administrations via a calibrated pipette. To standardize the amount of ointment administered, each ophthalmic ointment was first loaded into a tuberculin syringe (BD Medical, Holdrege, USA) and then extruded onto a flat surface to form a strip approximately 1 cm in length (corresponding to the manufacturer‐recommended ¼–½ inch strip), as measured by a ruler on the flat surface. This procedure was repeated 10 separate times to determine the volume required to generate a strip of this length. The volume needed to produce a ~1 cm strip averaged 0.05 mL. For all experiments, each ointment was subsequently loaded into a tuberculin syringe immediately prior to administration, and 0.05 mL was instilled onto the ocular surface.

2.4. Tear Collection and Drug Quantification

Tear fluid was collected from both eyes at baseline (0 min, defined as immediately after drug administration and spontaneous blinking), and subsequently at 1, 5, 10, 15, 30, 60, 120, 240, and 480 min post‐administration. The first sampling point (t = 0 min) represents the initial post‐administration tear concentration and served as the baseline for subsequent pharmacokinetic measurements. A 2‐μL microcapillary glass tube (Drummond Scientific Co., Broomall, PA, USA) was placed in contact with the inferior lacrimal lake for ≤ 5 s to collect tear fluid by capillary action, with care taken to minimize reflex tearing during sampling. Chloramphenicol concentrations were quantified using UV–Vis spectrophotometry (NanoDrop One; Thermo Fisher Scientific Inc., Waltham, MA, USA). Standard calibration curves were generated in blank tear fluid using known concentrations (0.01–30,000 μg/mL) of a chloramphenicol reference standard (Chloramphenicol USP; Sigma‐Aldrich, St. Louis, MO, USA); blank tears were collected from the same dogs prior to the experiment using ophthalmic sponges, as previously described (Sebbag et al. 2018; Sebbag, Kirner, et al. 2020). The calibration curve exhibited high linearity (R 2 = 0.999). Absorbance was measured at a wavelength of 278 nm, in accordance with previously validated methods for chloramphenicol stability and quantification (Abdel‐Hamid and Abuirjeie 1987; Szulczewski and Eng 1975). Based on the calibration curve generated in blank tear fluid and the background absorbance of the tear matrix, the estimated limit of detection (LOD) and limit of quantification (LOQ) for chloramphenicol were approximately 1 and 10 μg/mL, respectively; concentrations below the LOQ were considered non‐quantifiable for subsequent analyses.

2.5. Data Analysis

Data normality was assessed using the Shapiro–Wilk test. All variables were normally distributed (p ≥ 0.125) and are therefore reported as mean ± standard deviation. For each formulation (solution, ointment), changes in chloramphenicol tear concentrations over time were analyzed using two‐way repeated‐measures ANOVA and Bonferroni post hoc test, with Treatment and Time as within‐subject factors. The area under the curve from 0 to 480 min (AUC0–480) for chloramphenicol tear concentrations was calculated using the trapezoidal method and compared between eyes using paired t‐tests. Statistical analyses were performed using SigmaPlot version 15.0 (Systat Software Inc.), and p < 0.05 was considered statistically significant.

3. Results

No ocular or systemic adverse effects were observed in any of the dogs during or after administration of the study formulations, and all animals remained clinically normal throughout the experimental sessions.

3.1. Solution Formulations

Immediately following administration (t = 0 min), mean ± SD tear film concentrations were significantly higher following instillation of the 0.8% solution (4646 ± 716 μg/mL) compared with the 0.2% solution (1998 ± 356 μg/mL; p < 0.001). Tear concentrations remained significantly higher in the 0.8% group through 240 min post‐instillation (p ≤ 0.009; Figure 1). Overall drug exposure, expressed as AUC0–480, was 2.2‐fold higher for the 0.8% solution (184,202 ± 34,705 μg/mL·min) compared with the 0.2% solution (83,438 ± 17,419 μg/mL·min; p < 0.001).

FIGURE 1.

FIGURE 1

Open in a new tab

Mean ± SD concentrations of chloramphenicol (μg/mL) in tear fluid following a single administration of either 0.8% chloramphenicol solution (black circles; Crotax) or 0.2% chloramphenicol solution (white circles; Phenimixin) in 8 dogs (16 eyes). Significant differences between treatment groups at corresponding time points are indicated by an asterisk (*p < 0.05).

3.2. Ointment Formulations

At t = 0 min, mean ± SD tear film concentrations were significantly higher with the 5% ointment (29,421 ± 2525 μg/mL) than with the 1% ointment (7225 ± 903 μg/mL; p < 0.001). Tear concentrations remained significantly higher for the 5% formulation at 1, 5, 10, 15, 30, and 60 min post‐treatment (p ≤ 0.031), with no significant differences detected from 120 min onward (Figure 2). Consistent with these findings, AUC0–480 was 3.0‐fold higher in eyes treated with the 5% ointment (560,513 ± 53,258 μg/mL·min) compared with the 1% ointment (184,979 ± 18,497 μg/mL·min; p < 0.001).

FIGURE 2.

FIGURE 2

Open in a new tab

Mean ± SD concentrations of chloramphenicol (μg/mL) in tear fluid following a single administration of 5% chloramphenicol ointment (black circles; Synthomycin) or 1% chloramphenicol ointment (white circles; Crotax) in 8 dogs (16 eyes). Significant differences between treatment groups at corresponding time points are indicated by an asterisk (*p < 0.05).

3.3. Solution Versus Ointment

To compare tear film pharmacokinetics between vehicles, the 1% ointment was evaluated against the 0.8% solution (Figure 3). Mean ± SD tear concentrations were significantly higher with the ointment at t = 0 min (7225 ± 903 vs. 4646 ± 716 μg/mL; p < 0.001) and remained significantly higher at 1, 5, 10, and 15 min post‐administration (p ≤ 0.041). From 30 min onward, no statistically significant differences were detected between formulations (p ≥ 0.119). Overall drug exposure, expressed as AUC0–480, did not differ significantly between the 1% ointment (184,979 ± 18,497 μg/mL·min) and the 0.8% solution (184,202 ± 34,705 μg/mL·min; p = 0.961).

FIGURE 3.

FIGURE 3

Open in a new tab

Mean ± SD concentrations of chloramphenicol (μg/mL) in tear fluid following a single administration of 1% chloramphenicol ointment (black circles; Crotax) or 0.8% chloramphenicol solution (white circles; Crotax) in 8 dogs (16 eyes). Significant differences between treatment groups at corresponding time points are indicated by an asterisk (*p < 0.05).

4. Discussion

The present study confirms that both drug concentration and vehicle are major determinants of chloramphenicol exposure in the canine tear film. Across two paired‐eye crossover sessions, increasing solution concentration from 0.2% to 0.8% produced a 2.2‐fold rise in total tear exposure (AUC0–480), while increasing ointment concentration from 1% to 5% yielded a 3.0‐fold increase in exposure. These results reinforce a practical, clinically relevant concept: beyond antimicrobial spectrum, the ability of a formulation to establish and sustain tear film concentrations is a key driver of topical antibiotherapy performance in ophthalmology.

Higher concentrations predictably increased early tear concentrations and overall exposure, consistent with basic mass‐balance principles for topical dosing. Importantly, the magnitude of benefit differed by vehicle, likely reflecting the relative contribution of rapid precorneal elimination for solutions versus “reservoir” behavior for petrolatum‐based ointments (Hardberger et al. 1975; Bedos et al. 2023). Aqueous drops are cleared rapidly in dogs due to blink‐related loss and nasolacrimal drainage, with canine tear turnover being especially high under reflex conditions (Davies 2000; Sebbag, Allbaugh, et al. 2019; Sebbag, Soler, et al. 2020). Accordingly, a concentration‐based strategy can be particularly valuable when the drug is delivered in an aqueous vehicle that is otherwise prone to early loss. At the same time, the present data show that concentration also matters within ointments, supporting the concept that ointment performance is not solely a function of viscosity but also of the drug load available for release over time (Hardberger et al. 1975; Hyndiuk et al. 1988; Greaves et al. 1993). Importantly, the formulations were broadly comparable within each vehicle class. Both ointments used similar petrolatum‐based vehicles (white soft paraffin with lanolin), whereas the solutions consisted of conventional aqueous ophthalmic vehicles (e.g., buffered isotonic solutions containing water, tonicity‐adjusting agents, and pH stabilizers), suggesting that the observed pharmacokinetic differences were most likely driven primarily by chloramphenicol concentration and formulation type rather than major differences in excipient composition.

Notably, the increase in tear exposure was lower than the fold‐increase in nominal drug concentration (e.g., a 5‐fold increase in ointment concentration yielded a 3.0‐fold increase in AUC). Because the ointments had broadly similar petrolatum‐based vehicles, this discrepancy is unlikely to be explained primarily by excipient differences. Instead, it likely reflects the non‐linear nature of ocular surface pharmacokinetics, where finite tear film volume, rapid precorneal loss, and non‐linear drug release from the ointment matrix limit proportional increases in tear exposure with higher drug loading. Similar principles likely contribute to the less‐than‐proportional increase observed between the two solution formulations.

A key observation was the persistence of quantifiable tear concentrations at 8 h for both ointment formulations, in contrast to aqueous solutions, which fell below the limit of quantification by the final time point. Similar findings have been reported previously, where tear concentrations were low (mean 3.3 μg/mL) 8 h after administration of a 1% prednisolone acetate ophthalmic solution in dogs, which would fall below the limit of quantification in the present study (Sebbag, Kirner, et al. 2020). Here, the 1% and 5% ointments maintained mean tear concentrations of 17.9 and 88.7 μg/mL, respectively, at 480 min post‐administration, values that exceed the minimal inhibitory concentrations reported for many common canine (Hewitt et al. 2020; Jinks et al. 2020) and human (Robert and Adenis 2001) ocular pathogens. This finding is consistent with the known ability of petrolatum‐based vehicles to prolong ocular surface residence and reduce immediate precorneal drainage, as demonstrated in a canine fluorophotometric study comparing ointment and solution lubricants (Bedos et al. 2023). Similar patterns of enhanced surface persistence with ointments have been reported in human and rabbit models (Hardberger et al. 1975; Greaves et al. 1993; Hyndiuk et al. 1988). This advantage should be interpreted cautiously. Ointment formulations do not prevent rapid early drug loss from the ocular surface; rather, they achieve higher initial tear concentrations and permit measurable drug levels to persist for longer durations, without fundamentally altering the overall kinetic pattern. This distinction is clinically relevant when counseling owners and setting realistic expectations for dosing intervals in active keratoconjunctivitis, a condition in which tear turnover and precorneal clearance are often further amplified (Sebbag and Mochel 2020; Sebbag, Kirner, et al. 2020).

Despite higher early concentrations with the 1% ointment, overall exposure did not differ between the 0.8% solution and 1% ointment. This finding suggests that, over an 8‐h interval in healthy eyes, a relatively concentrated solution can yield comparable cumulative exposure to a low‐concentration ointment, even if early tear concentrations differ. Practically, it supports flexibility in formulation choice when similar‐strength products are available and owner administration preferences differ, while still recognizing that ointments can provide higher measurable concentrations at late time points. Interpretation of this comparison should also consider dose standardization: the solution volume was fixed at ~41 μL in the present study, while ointment dosing was standardized to a ~1 cm strip (~0.4 in.). Because excess solution volume beyond ocular surface capacity is rapidly lost to drainage and periocular spillage (Sebbag, Kirner, et al. 2019), increasing “dose” by adding additional drops is often inefficient (Sebbag, Allbaugh, et al. 2019; Page et al. 2023). By contrast, ointment can function as a local depot, so modest differences in administered amount (e.g., 2 cm strip) may translate into measurable exposure differences, a speculation that should be verified in future studies.

A common hesitation in clinical practice is the concern that ointment vehicles might delay corneal epithelialization by creating a mechanical barrier to cell migration. Available experimental evidence does not support this concern. In rabbits, chloramphenicol drops and ointment showed no difference in healing rates of corneal erosions (Barequet et al. 2014), and ofloxacin ointment did not retard re‐epithelialization compared with solution in corneal wound models (Fujihara et al. 1993). These data suggest that, when an antibiotic is otherwise appropriate, the choice between ointment and solution should be guided more by expected ocular surface exposure, patient tolerance, and owner feasibility than by fear of delayed healing.

In real‐world canine keratitis, owners often struggle with frequent dosing, and dogs may resist repeated administration. The present data provide pharmacokinetic support for strategies that maximize tear film exposure per administration: higher concentration when available, and ointment vehicles when feasible. For example, in the authors' country of profession, chloramphenicol exists commercially in all four formulations examined here; therefore, the 5% ophthalmic ointment is often favored when owner administration is feasible. Importantly, this should not be interpreted as a rigid dosing algorithm. Owner preference, patient temperament, and product availability often dictate what can realistically be administered.

From a pharmacokinetic‐pharmacodynamic (PK‐PD) perspective, topical antibiotic efficacy is commonly interpreted using indices such as the percent time above the minimal inhibitory concentration (%T > MIC) for time‐dependent antibiotics and the AUC:MIC ratio for concentration‐dependent agents (Rodríguez‐Gascón et al. 2021; Toutain et al. 2021). Increasing ocular surface exposure (e.g., 5% versus 1% chloramphenicol ointment) may therefore improve these PK‐PD indices by prolonging the duration that tear concentrations remain above bacterial MICs and by increasing overall drug exposure. While this concept is particularly relevant for time‐dependent antibiotics such as chloramphenicol, it may also apply more broadly to other ophthalmic antimicrobials.

Several limitations should be acknowledged. First, 0.2% chloramphenicol solution was co‐formulated with polymyxin B, whereas the other formulations contained chloramphenicol alone. Analytical interference is unlikely because chloramphenicol was quantified at 278 nm, while polymyxin B is typically detected at substantially lower UV wavelengths (~210 nm); similar antibiotic quantification has been reported in ophthalmic formulations containing polymyxin B (Sigmund et al. 2020). Nevertheless, because the potential effect of polymyxin B on formulation behavior or ocular surface pharmacokinetics was not specifically evaluated, its contribution cannot be completely excluded. Second, this study was conducted in young, healthy dogs, whereas bacterial keratitis is generally associated with marked alterations in tear composition, turnover, and barrier integrity. Breakdown of the blood‐tear barrier in diseased eyes leads to increased tear albumin concentrations, and because only the unbound fraction of an antibiotic is microbiologically active, protein binding may reduce effective drug availability (Sebbag et al. 2021; Kubai et al. 2024). Excessive lacrimation in infected eyes may further dilute the medication, potentially increasing the value of higher‐concentration formulations and depot‐like vehicles in diseased eyes. For these reasons, PK‐PD indices were not calculated and dosing recommendations were intentionally avoided in the present study, as tear turnover, inflammation, and protein binding in healthy eyes differ substantially from those encountered in clinical bacterial keratitis. Third, this study quantified total drug concentrations but did not assess free drug fractions, corneal tissue penetration, aqueous humor levels, or clinical outcomes. Further, although administration volumes were standardized, real‐world variability in dosing technique and tear dynamics will inevitably affect ocular surface exposure. Finally, tear fluid was collected using microcapillary tubes, a method selected because it minimizes reflex tearing and removes only very small tear volumes, thereby limiting disruption of tear film dynamics and allowing repeated sampling after a single administration (Arad et al. 2026), unlike Schirmer tear strips which absorb a larger fraction of the tear film (Sebbag, Kirner, et al. 2020; Pe'er et al. 2025). Nevertheless, this sampling approach could theoretically influence measured concentrations, particularly with viscous formulations such as ointments. Subjectively, tear sampling was technically more challenging following ointment administration than after solutions due to the presence of the petrolatum‐based vehicle on the ocular surface, although sufficient tear volume for drug quantification was obtained in all cases. Chloramphenicol is a relatively lipophilic compound that mixes readily within petrolatum‐based ointment formulations (Robert and Adenis 2001), suggesting relatively homogeneous distribution within the ointment matrix; however, the extent to which tear sampling reflects freely dissolved drug may differ for compounds with other physicochemical properties.

5. Conclusion

This study demonstrates that chloramphenicol exposure in canine tear film is strongly influenced by both drug concentration and formulation. Higher concentration increases total exposure in solutions and ointments, and ointments maintain quantifiable tear levels later than solutions, with the 5% ointment providing the greatest overall exposure and late‐timepoint concentrations. These findings provide a clear pharmacokinetic framework for understanding how “what is applied” (concentration) and “how it is applied” (vehicle) shape ocular surface exposure. In other words, when managing bacterial keratitis, how an antibiotic is delivered can be as important as which antibiotic is selected.

Author Contributions

Bar Fruchter: writing – original draft, data curation and writing – review and editing. Oren Pe'er: writing – review and editing. Shir Gonen: data curation. Lionel Sebbag: conceptualization, writing – original draft, formal analysis, writing – review and editing, supervision. All authors have read and agreed to the published version of the manuscript.

Ethics Statement

This study was approved by the Institutional Animal Care and Use Committee of Israel's Ministry of Health (protocol # 2510–415‐2).

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

The authors thank Orna Braun and the Israeli Guide Dog Center for the Blind for making their dogs available for this study.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Abdel‐Hamid, M. E. , and Abuirjeie M. A.. 1987. “Spectrophotometric Determination of Chloramphenicol Using Orthogonal Polynomials.” Analyst 112, no. 6: 895–897. [DOI] [PubMed] [Google Scholar]
  2. Arad, D. , Mordechai E. M., Goncharov Y., Ofri R., and Sebbag L.. 2026. “Enhanced Tear Film Concentrations of Cefazolin and Chloramphenicol Using Cross‐Linked Hyaluronic Acid in Canine Eyes.” Veterinary Ophthalmology 29, no. 1: e70013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bale, B. I. , Elebesunu E. E., Manikavasagar P., et al. 2023. “Antibiotic Resistance in Ocular Bacterial Infections: An Integrative Review of Ophthalmic Chloramphenicol.” Tropical Medicine and Health 51, no. 1: 15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barequet, I. S. , Harizman N., Ziv H., and Rosner M.. 2014. “Healing Rate of Corneal Erosions: Comparison of the Effect of Chloramphenicol Eye Drops and Ointment and High‐Concentration Hyaluronic Acid in an Animal Model.” Cornea 33, no. 10: 1080–1082. [DOI] [PubMed] [Google Scholar]
  5. Bedos, L. , Allbaugh R. A., Roy M., Kubai M. A., and Sebbag L.. 2023. “Precorneal Retention Time of Ocular Lubricants Measured With Fluorophotometry in Healthy Dogs.” Veterinary Ophthalmology 26, no. Suppl 1: 81–88. [DOI] [PubMed] [Google Scholar]
  6. Casemiro, P. A. , Andrade A. L., Cardozo M. V., et al. 2025. “Prevalence and Antibiotic Resistance in Bacterial Isolates of Dogs With Ulcerative Keratitis in São Paulo State, Brazil.” Veterinary Ophthalmology 28, no. 1: 37–47. [DOI] [PubMed] [Google Scholar]
  7. Davies, N. M. 2000. “Biopharmaceutical Considerations in Topical Ocular Drug Delivery.” Clinical and Experimental Pharmacology and Physiology 27, no. 7: 558–562. 10.1046/j.1440-1681.2000.03288.x. [DOI] [PubMed] [Google Scholar]
  8. Fujihara, T. , Nakano T., and Hikida M.. 1993. “Effect of Ofloxacin Eye Drops and Eye Ointment on Corneal Re‐Epithelialization.” Journal of Toxicology‐Cutaneous and Ocular Toxicology 12, no. 1: 67–73. [Google Scholar]
  9. Greaves, J. L. , Wilson C. G., and Birmingham A. T.. 1993. “Assessment of the Precorneal Residence of an Ophthalmic Ointment in Healthy Subjects.” British Journal of Clinical Pharmacology 35, no. 2: 188–192. [PMC free article] [PubMed] [Google Scholar]
  10. Hardberger, R. , Hanna C., and Boyd C. M.. 1975. “Effects of Drug Vehicles on Ocular Contact Time.” Archives of Ophthalmology 93, no. 1: 42–45. [DOI] [PubMed] [Google Scholar]
  11. Hewitt, J. S. , Allbaugh R. A., Kenne D. E., and Sebbag L.. 2020. “Prevalence and Antibiotic Susceptibility of Bacterial Isolates From Dogs With Ulcerative Keratitis in Midwestern United States.” Frontiers in Veterinary Science 7: 583965. 10.3389/fvets.2020.583965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hindley, K. E. , Groth A. D., King M., Graham K., and Billson F. M.. 2016. “Bacterial Isolates, Antimicrobial Susceptibility, and Clinical Characteristics of Bacterial Keratitis in Dogs Presenting to Referral Practice in Australia.” Veterinary Ophthalmology 19, no. 5: 418–426. [DOI] [PubMed] [Google Scholar]
  13. Hyndiuk, R. A. , Skorich D. N., Davis S. D., Sarff L. D., Divine K., and Burd E.. 1988. “Fortified Antibiotic Ointment in Bacterial Keratitis.” American Journal of Ophthalmology 105, no. 3: 239–243. [DOI] [PubMed] [Google Scholar]
  14. Jinks, M. R. , Miller E. J., Diaz‐Campos D., et al. 2020. “Using Minimum Inhibitory Concentration Values of Common Topical Antibiotics to Investigate Emerging Antibiotic Resistance: A Retrospective Study of 134 Dogs and 20 Horses With Ulcerative Keratitis.” Veterinary Ophthalmology 23, no. 5: 806–813. [DOI] [PubMed] [Google Scholar]
  15. Kubai, M. A. , Roy M. M., Stinman C. C., Kenne D. E., Allbaugh R. A., and Sebbag L.. 2024. “Topical Blood Products Modulate the Effects of Ophthalmic Antibiotics Against Common Bacterial Pathogens in Dogs With Infectious Keratitis.” Frontiers in Veterinary Science 11: 1417842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ollivier, F. J. 2003. “Bacterial Corneal Diseases in Dogs and Cats.” Clinical Techniques in Small Animal Practice 18, no. 3: 193–198. [DOI] [PubMed] [Google Scholar]
  17. Page, L. E. , Kubai M. A., Allbaugh R. A., et al. 2023. “Increased Drug Concentration and Repeated Eye Drop Administration as Strategies to Optimize Topical Drug Delivery: A Fluorophotometric Study in Healthy Dogs.” Veterinary Ophthalmology 26, no. 4: 331–338. 10.1111/vop.13061. [DOI] [PubMed] [Google Scholar]
  18. Pe'er, O. , Thomasy S. M., Feuer E., Knych H. K., Ofri R., and Sebbag L.. 2025. “Ocular Tolerance and Tear Film Pharmacokinetics of 1% Penciclovir Cream in Cats.” Research in Veterinary Science 196: 105909. 10.1016/j.rvsc.2025.105909. [DOI] [PubMed] [Google Scholar]
  19. Robert, P. Y. , and Adenis J. P.. 2001. “Comparative Review of Topical Ophthalmic Antibacterial Preparations.” Drugs 61, no. 2: 175–185. 10.2165/00003495-200,161,020-00003. [DOI] [PubMed] [Google Scholar]
  20. Rodríguez‐Gascón, A. , Solinís M., and Isla A.. 2021. “The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials.” Pharmaceutics 13, no. 6: 833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sebbag, L. , Allbaugh R. A., Wehrman R. F., et al. 2019. “Fluorophotometric Assessment of Tear Volume and Turnover Rate in Healthy Dogs and Cats.” Journal of Ocular Pharmacology and Therapeutics 35, no. 9: 497–502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sebbag, L. , Broadbent V. L., Kenne D. E., Perrin A. L., and Mochel J. P.. 2021. “Albumin in Tears Modulates Bacterial Susceptibility to Topical Antibiotics in Ophthalmology.” Frontiers in Medicine 8: 663212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sebbag, L. , Harrington D. M., and Mochel J. P.. 2018. “Tear Fluid Collection in Dogs and Cats Using Ophthalmic Sponges.” Veterinary Ophthalmology 21, no. 3: 249–254. 10.1111/vop.12502. [DOI] [PubMed] [Google Scholar]
  24. Sebbag, L. , Kirner N. S., Allbaugh R. A., Reis A., and Mochel J. P.. 2019. “Kinetics of Fluorescein in Tear Film After Eye Drop Instillation in Beagle Dogs: Does Size Really Matter?” Frontiers in Veterinary Science 6: 457. 10.3389/fvets.2019.00457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sebbag, L. , Kirner N. S., Wulf L. W., and Mochel J. P.. 2020. “Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs.” Frontiers in Veterinary Science 7: 571350. 10.3389/fvets.2020.571350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sebbag, L. , and Mochel J. P.. 2020. “An Eye on the Dog as the Scientist's Best Friend for Translational Research in Ophthalmology: Focus on the Ocular Surface.” Medicinal Research Reviews 40, no. 6: 2566–2604. 10.1002/med.21716. [DOI] [PubMed] [Google Scholar]
  27. Sebbag, L. , Soler E. A., Allbaugh R. A., and Mochel J. P.. 2020. “Impact of Acute Conjunctivitis on Ocular Surface Homeostasis in Dogs.” Veterinary Ophthalmology 23, no. 5: 828–833. [DOI] [PubMed] [Google Scholar]
  28. Sigmund, A. B. , Ward D. A., Cox S. K., and Hendrix D. V. H.. 2020. “Tear Film Concentrations of Topically Applied 0.5% Oxytetracycline Ointment in Normal Canine Eyes.” Veterinary Ophthalmology 23, no. 4: 707–713. 10.1111/vop.12783. [DOI] [PubMed] [Google Scholar]
  29. Szulczewski, D. , and Eng F.. 1975. “Chloramphenicol.” In Analytical Profiles of Drug Substances, vol. 4, 47–90. Academic Press. [Google Scholar]
  30. Tolar, E. L. , Hendrix D. V., Rohrbach B. W., Plummer C. E., Brooks D. E., and Gelatt K. N.. 2006. “Evaluation of Clinical Characteristics and Bacterial Isolates in Dogs With Bacterial Keratitis: 97 Cases (1993–2003).” Journal of the American Veterinary Medical Association 228, no. 1: 80–85. 10.2460/javma.228.1.80. [DOI] [PubMed] [Google Scholar]
  31. Toutain, P. L. , Pelligand L., Lees P., Bousquet‐Mélou A., Ferran A. A., and Turnidge J. D.. 2021. “The Pharmacokinetic/Pharmacodynamic Paradigm for Antimicrobial Drugs Inveterinary Medicine: Recent Advances and Critical Appraisal.” Journal of Terinary Pharmacology and Therapeutics 44, no. 2: 172–200. [DOI] [PubMed] [Google Scholar]
  32. Tsvetanova, A. , Powell R. M., Tsvetanov K. A., Smith K. M., and Gould D. J.. 2021. “Melting Corneal Ulcers (Keratomalacia) in Dogs: A 5‐Year Clinical and Microbiological Study (2014–2018).” Veterinary Ophthalmology 24, no. 3: 265–278. 10.1111/vop.12885. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Articles from Journal of Veterinary Pharmacology and Therapeutics are provided here courtesy of Wiley

RESOURCES