Does orally administered doxycycline reach the tear film?

Smith, Valerie; Khan-Lim, Doreen; Cook, Stuart D.; Dick, Andrew D.

doi:10.1136/bjo.2007.125989

Cited by 37 publications

(27 citation statements)

References 24 publications

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“…These effects are believed to occur at concentrations lower than those required for antimicrobial activity. For example, in a recent study, 36 oncedaily oral administration of 100 mg of doxycycline to humans did not produce detectable tear doxycycline concentrations but did reduce the tear matrix metalloproteinase-9 concentrations that are responsible for disease progression. Although antiprotease and antiinflammatory activity was not tested in that study, 36 multiple other studies 37,38 indicate that doxycycline, even at subantimicrobial concentrations, has important anti-inflammatory and anti-matrix metalloproteinase activity in people.…”

Section: Discussionmentioning

confidence: 97%

“…For example, in a recent study, 36 oncedaily oral administration of 100 mg of doxycycline to humans did not produce detectable tear doxycycline concentrations but did reduce the tear matrix metalloproteinase-9 concentrations that are responsible for disease progression. Although antiprotease and antiinflammatory activity was not tested in that study, 36 multiple other studies 37,38 indicate that doxycycline, even at subantimicrobial concentrations, has important anti-inflammatory and anti-matrix metalloproteinase activity in people. Thus, it is likely that the doxycycline concentrations achieved in the tear film of northern elephant seals in the present study receiving 10 or 20 mg of doxycycline/kg would be expected to exert anti-inflammatory, antiprotease, or other nonmicrobial therapeutic activities.…”

Section: Discussionmentioning

confidence: 97%

“…Doxycycline blocks interleukin-1 and thus matrix metalloproteinase-9 synthesis, reducing clinical signs associated with keratoconjunctivitis sicca, meibomitis, and infected and noninfected corneal ulcers; improves corneal smoothness; and permits corneal re-epithelialization. 36,37 An ability to reduce matrix metalloproteinase activity is especially important because these proteases promote collagenolysis and lead to corneal matrix degradation, corneal malacia, and potentially globe rupture. These effects are believed to occur at concentrations lower than those required for antimicrobial activity.…”

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Freeman¹,

Thomasy²,

Stanley³

et al. 2013

javma

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Objective-To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris). Design-Pharmacokinetic study. Animals-18 juvenile northern elephant seals without signs of ocular disease. Procedures-Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis. Results-Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 µg/mL at 6.1 hours on day 1 and was 1.5 µg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 µg/mL at 2.3 hours on day 1 and 1.9 µg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing. Conclusions and Clinical Relevance-Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species. (J Am Vet

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Freeman¹,

Thomasy²,

Stanley³

et al. 2013

javma

View full text Add to dashboard Cite

show abstract

“…Doxycycline has both antibiotic and anti-inflammatory properties. The latter is due to the inhibition of matrix metalloproteinase and IL-1 activity [68] [69].…”

Section: ) For the Prevention Of Tear Evaporationmentioning

confidence: 99%

Ocular Graft versus Host Disease: A Review of Clinical Manifestations, Diagnostic Approaches and Treatment

Nair¹,

Vanathi²,

Ganger³

et al. 2016

OJOph

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Allogenic haematological stem cell transplantation (allo-SCT) from a human leukocyte antigen (HLA) matched related or unrelated donor is used as a curative therapy for a large number of malignant and non-malignant haematological diseases. The curative effect of allo-SCT is achieved by graft versus leukaemia effect while the downside of the graft versus patient activity is the graftversus-host-disease (GVHD), a major reason for mortality and morbidity. The search of articles for this review had been accomplished using Ovid, Medline, Embase, Pubmed and was supplemented by retrieving cross references also. Electronic literature search for English language articles with full text access was performed using graft versus host disease, ocular, management, dry eyes as key words. This review has been intended to explicate the classification, pathogenesis, risk factors and management of ocular graft versus host disease.

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“…3 Smith et al 4 revealed that though oral DC does not reach tear film, it indirectly inhibits matrix metalloproteinases or the synthesis of these enzymes and interleukin-1 from corneal epithelial cells. Also Salminen 5 reported good penetrability of parenteral DC into the ocular compartments including cornea due to it's lipophilic nature.…”

mentioning

confidence: 99%

Re: The Beneficial Effects of Doxycycline, an Inhibitor of Matrix Metalloproteinases, on Sulfur Mustard-induced Ocular Pathologies Depend on the Injury Stage

İlhan

Yolcu

Gündoğan

2014

Current Eye Research

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Does orally administered doxycycline reach the tear film?

Abstract: The inability to detect doxycycline in the tear film of patients undergoing treatment indicates that doxycycline does not directly inhibit MMP activity or the synthesis/secretion of these proteases and IL-1 from corneal epithelial cells.

Cited by 37 publications

References 24 publications

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Ocular Graft versus Host Disease: A Review of Clinical Manifestations, Diagnostic Approaches and Treatment

Re: The Beneficial Effects of Doxycycline, an Inhibitor of Matrix Metalloproteinases, on Sulfur Mustard-induced Ocular Pathologies Depend on the Injury Stage

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