Vitreous and subretinal fluid concentrations of orally administered dabigatran in patients with rhegmatogenous retinal detachment

Verena C Mulder, Cornelis Kluft, Jan C van Meurs

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: One of the factors that was shown to contribute to the development of proliferative vitreoretinopathy (PVR) is the coagulation factor thrombin. Therefore, a specific oral thrombin inhibitor such as dabigatran might be a possible therapeutic option. An oral drug has the advantage of patient-friendly prolonged administration in contrast to drugs that can only be applied during vitrectomy, on condition that the drug reaches the target site. We tested whether dabigatran reaches the vitreous and subretinal fluid (SRF) after a single oral dose of dabigatran.

METHODS: Twenty-eight patients with a retinal detachment received a single dose of 220 mg dabigatran etexilate 2-8 hr prior to surgery. During surgery, we took a blood sample and a vitreous or subretinal fluid sample. The concentration of dabigatran was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS: The dabigatran concentration between 2 and 9 hr after administration was higher in SRF than in vitreous (max 8.5 and 3.8 ng/ml). Corresponding plasma concentrations ranged from 15 to 225 ng/ml. There was a significant relationship between SRF levels and plasma levels (rs = 0.68, p = 0.014); the levels in vitreous fluid showed no such relationship (rs = 0.20, p = 0.48). In addition, we measured the vitreous concentration of a non-study patient using 150 mg dabigatran twice daily. The concentration was approximately 10 times higher than after a single dosage (25.8 ng/ml).

CONCLUSION: We demonstrate that oral intake of dabigatran, a candidate drug to modulate PVR, results in potentially relevant intraocular concentrations. We suggest that repeated dosing may lead to higher concentrations, but this should be further explored.

Original languageEnglish
Pages (from-to)663-667
Number of pages5
JournalActa Ophthalmologica
Issue number7
Publication statusPublished - Nov 2016


  • Administration, Oral
  • Adult
  • Aged
  • Antithrombins/administration & dosage
  • Chromatography, Liquid
  • Dabigatran/administration & dosage
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retinal Detachment/metabolism
  • Subretinal Fluid/metabolism
  • Tandem Mass Spectrometry
  • Tissue Distribution
  • Vitreous Body/metabolism


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