Abstract
Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at selected times. Prednisone and prednisolone were quantified in tears by liquid chromatography-mass spectrometry.Results: Lacrimal prednisone and prednisolone concentrations ranged from 2 to 523 ng/mL and 5 to 191 ng/mL, respectively. Drug concentrations were overall greater in dogs receiving higher doses of prednisone, but were not correlated with tear flow rate. Eyes with conjunctivitis often had larger amounts of prednisone and prednisolone in tear fluid compared to control eyes (up to +64%), but differences were not statistically significant. Significantly greater, but clinically insignificant, levels of prednisolone were found in eyes with severe versus mild conjunctivitis for oral prednisone doses ≥1.0 mg/kg.Conclusions: Disruption of the blood–tear barrier with conjunctivitis did not significantly affect drug levels in tears. Based on drug PK in tears, oral prednisone is likely safe for the management of reflex uveitis and ocular surface diseases. However, further prospective trials using systemic corticotherapy in diseased animals are warranted to confirm findings from this preclinical study.
Highlights
Prednisone is a corticosteroid with a wide range of pharmacological indications that is commonly used for the treatment of inflammatory and immune-mediated diseases in human and veterinary medicine
Following oral administration of prednisone, both prednisone and prednisolone were quantifiable in tear fluid, with concentrations ranging from 2 to 523 ng/mL and 5 to 191 ng/mL, respectively
Eyes with conjunctivitis showed a trend for larger concentrations of prednisone and prednisolone in tear fluid compared with control eyes (Figs. 2 and 3), with differences in average concentrations ranging from +5% to +64%
Summary
Prednisone is a corticosteroid with a wide range of pharmacological indications that is commonly used for the treatment of inflammatory and immune-mediated diseases in human and veterinary medicine. Corticosteroids can alleviate ocular inflammation and help prevent devastating sequelae that could be painful or vision threatening.[1] Of the various routes of administration, systemic therapy is generally recommended when the target tissue cannot be reached with topical ophthalmic corticosteroids (eg, eyelids, posterior segment, orbit), or as a complement to topical medications in cases of anterior uveitis.[2]. Administered medications can readily distribute to the vascular tissues of the eye but can affect the ocular surface if the drug reaches the tear compartment. Oral doxycycline can be used as adjunctive therapy for keratomalacia in dogs and horses,[3,4] while oral famciclovir is highly effective in managing herpetic keratoconjunctivitis in cats.[5,6]
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