Subconjunctival penetration and aqueous pharmacokinetics of tissue plasminogen activator in presence and absence of fibrin

C. J. Ruiz-Lapuente, A. Martinez-Palmer, G. A. Peyman, M. R. Castilla, D. Nahra

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    Purpose. Tissue plasminogen activator (rt-PA) has been used for several ophthalmic indications with intraocular fibrin formation. Nevertheless, further knowledge of the pharmacokinetics of rt-PA directly injected into the anterior chamber or subconjunctivally delivered both in the presence and absence of fibrin is needed for dosage adjustment. Methods. We used 97 eyes of albino New Zealand rabbits weighing 2.5-3.5 kg that were assigned to any of 4 groups (A, B, C, D, n=24 each) and 1 control. Eyes of group A underwent subconjunctival injection of rt-PA (300 μg in mL). Eyes of group B prior to the same treatment received 0.1 mL of autologous plasma into the anterior chamber. Group C was injected with 10 μg rt-pA in 0.1 mL and Group D received the same treatment as C after autologous plasma injection. Rabbits were sacrificed at 30, 60, 120, 240 min, 12 and 24 h and aqueous was frozen for ELISA rt-PA determinations. Results. Maximum levels of rt-PA were achieved by anterior chamber injection of 10 μg in the absence of fibrin peaking at 30 min (mean 3848 ng/mL) but subconjunctival penetration reached therapeutic levels (mean 887.5 ng/mL). Groups B and D showed lower levels of rt-PA at the early times. A control was analyzed, revealing 0.83 ng/mL. Conclusions. Subconjunctival delivery of rt-PA is an alternative treatment for intraocular fibrinolysis. Levels of rt-PA decay after 2 h. The presence of fibrin seems to reduce ELISA levels of rt-PA. Repeated intraocular injections of rt-PA should be considered when needed.
    Original languageEnglish
    JournalInvestigative Ophthalmology and Visual Science
    Issue number3
    Publication statusPublished - 15 Feb 1996


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