期刊
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
卷 27, 期 4, 页码 359-364出版社
SPRINGER
DOI: 10.1007/s11239-008-0230-1
关键词
Clinical trials; Myocardial infarction; Reperfusion injury; Poly(ADP-ribose) polymerase
资金
- NHLBI NIH HHS [R44 HL074684-01] Funding Source: Medline
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 (t(1/2)) 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.
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