Abstract
Background: Reperfusion injury is a significant complication of the management of ST-elevation MI (STEMI). INO-1001 is a potent inhibitor of poly(ADP-ribose) polymerase (PARP), a mediator of oxidant-induced myocyte dysfunction during reperfusion. Methods & results: We assessed the safety and pharmacokinetics of INO-1001 in a randomized, placebo-controlled, single-blind, dose-escalating trial in 40 patients with STEMI undergoing primary percutaneous coronary intervention within 24 h of onset. INO-1001 was well-tolerated. A trend toward more frequent transaminitis was observed with 800 mg. Plasma from INO1001-treated patients reduced in vitro PARP activity >90% at all doses. Serial C-reactive protein and IL-6 levels showed a trend toward blunting of inflammation with INO-1001. The apparent median terminal half-life (t1/2) of INO-1001 was 7.5 (25th, 75th: 5.9, 10.2) h. Conclusions: The results from this first trial of INO-1001 in STEMI support future investigation of INO-1001 as a novel treatment for reperfusion injury.
Original language | English |
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Pages (from-to) | 359-364 |
Number of pages | 6 |
Journal | Journal of Thrombosis and Thrombolysis |
Volume | 27 |
Issue number | 4 |
DOIs | |
State | Published - 2009 |
Externally published | Yes |
Keywords
- Clinical trials
- Myocardial infarction
- Poly(ADP-ribose) polymerase
- Reperfusion injury