title: Vitreous and subretinal fluid concentrations of orally administered dabigatran in patients with rhegmatogenous retinal detachment.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Rotterdam Ophthalmic Institute, Rotterdam Eye Hospital, Rotterdam, The Netherlands. v.mulder@oogziekenhuis.nl.
authors: Verena C
authors: VC
authors: Mulder
authors: Good Biomarker Sciences, Leiden, The Netherlands.
authors: Cornelis
authors: C
authors: Kluft
authors: Rotterdam Ophthalmic Institute, Rotterdam Eye Hospital, Rotterdam, The Netherlands.|Erasmus Medical Centre, Rotterdam, The Netherlands.
authors: Jan C
authors: JC
authors: van Meurs
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D000069604:Dabigatran / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012163:Retinal Detachment / Q000378:metabolism* / Q000601:surgery; D058471:Subretinal Fluid / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: dabigatran; proliferative vitreoretinopathy; retinal detachment; subretinal fluid; vitreous