AGI-1067: a novel vascular protectant for prevention of restenosis.
OBJECTIVE
To review the synthesis, pharmacology, clinical trials, and adverse effects of AGI-1067, a novel agent for preventing restenosis.


METHODS
Literature searches were conducted using MEDLINE (1966-July 2005) and International Pharmaceutical Abstracts (1970-July 2005) for English-language articles containing the search terms AGI-1067, AGI 1067, and probucol. In addition, bibliographies from relevant articles were reviewed for additional references.


METHODS
All articles identified from data sources were reviewed for relevant information. Applicable information was included in this review.


RESULTS
AGI-1067, a derivative of the lipid-lowering agent probucol, is the first of a new class of drugs termed vascular protectants. It has antioxidant and lipid-lowering effects. In addition, it inhibits inflammatory processes without resultant immunosuppression through its selective inhibition of vascular cell adhesion molecule-1 expression. AGI-1067 also exhibited anti-atherosclerotic effects in preclinical studies. Relatively short-term treatment with AGI-1067 showed positive results compared with probucol in preventing restenosis in patients undergoing percutaneous coronary intervention. AGI-1067 appears to be well tolerated and holds important advantages over probucol in that it has fewer adverse effects on high-density lipoprotein cholesterol and the QT interval.


CONCLUSIONS
The favorable safety profile of AGI-1067 offers potential advantages over its precursor, probucol. Preclinical and clinical studies indicate that it possesses antioxidant, antiinflammatory, and lipid-lowering properties. Ongoing Phase II and III studies will determine AGI-1067's place in therapy for the prevention of restenosis and reduction in cardiovascular events in patients undergoing percutaneous intervention for coronary atherosclerosis.
Franks
Amy M
AM
Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. afranks@uams.edu
Gardner
Stephanie F
SF
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D023903:Coronary Restenosis / Q000188:drug therapy / Q000517:prevention & control*; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D011341:Probucol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D015507:Drugs, Investigational; C471047:succinobucol; D011341:Probucol