title: Vitreous levels of active ocriplasmin following intravitreal injection: results of an ascending exposure trial.
abstract: OBJECTIVE
  To characterize the levels of active ocriplasmin over a period of ascending time points (range, 5 minutes to 7 days) from intravitreal injection of a 125-μg dose to sampling.
  
  
  METHODS
  During this 7-week controlled, open-label, phase 2 study, a single intravitreal (125 μg) dose of ocriplasmin was injected into the midvitreous of one eye of each of 34 patients prior to their scheduled primary pars plana vitrectomy. Patients were allocated to vitreous sampling at the beginning of the surgery, which occurred 5 to 30 minutes, 31 to 60 minutes, 2 to 4 hours, 24 ± 2 hours, or 7 ± 1 days after ocriplasmin injection, or to the control group, who received no ocriplasmin injection.
  
  
  RESULTS
  With increasing time from ocriplasmin injection to vitreous sampling, mean active ocriplasmin concentration decreased. While at 5 to 30 minutes postinjection, mean active ocriplasmin concentration was 11,597.7 ng/mL, within 31 to 60 minutes from injection the mean active ocriplasmin concentration had reduced to 8108.7 ng/mL; and by 24 hours after injection, half of the patients (2/4) had active ocriplasmin concentrations below the lower limit of quantification (LLQ; <272.4 ng/mL), as did all samples from the day 7 and control groups. No ocular serious adverse events (SAEs) were reported in patients who received ocriplasmin, while three ocular SAEs occurred in the study eye of one patient in the control group (1/38; 2.6%).
  
  
  CONCLUSIONS
  Active ocriplasmin concentrations in vitreous samples decreased with increasing time from injection to sample, with enzyme levels in all of the patients in the day 7 group being comparable to those in the control group. (ClinicalTrials.gov number, NCT01159665.).
authors: Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.
authors: Peter
authors: P
authors: Stalmans
authors: Aniz
authors: A
authors: Girach
mesh_terms: D000368:Aged; D005260:Female; D005341:Fibrinolysin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012164:Retinal Diseases / Q000188:drug therapy*; D013997:Time Factors; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C054561:microplasmin; D010447:Peptide Hydrolases; D005341:Fibrinolysin
keywords: intravitreal injection; ocriplasmin; persistent vitreomacular adhesion; vitrectomy; vitreomacular traction