Submitted on January 16, 2008
Revised on March 6, 2008
Accepted on March 6, 2008
Safety, pharmacokinetics and pharmacodynamics of a single dose of oral apolipoprotein A-I mimetic peptide D-4F in high-risk cardiovascular patients
LeAnne Bloedon, Richard Dunbar, Danielle Duffy, Paula Pinell-Salles, Robert Norris, Bruce J. DeGroot, Rajesh Movva, Mohamad Navab, Alan M. Fogelman, and Daniel J. Rader
Medicine, Univ Penn, Philadelphia, PA 19104-6160
Corresponding Author: rader{at}mail.med.upenn.edu
Patients with coronary heart disease or equivalent risk received a single dose of 30, 100, 300, or 500 mg of unformulated D-4F (n=8, each dose) or placebo (n=8) under fasting conditions. An additional 10 patients received 500 mg (n=8) or placebo (n=2) with a low fat meal. There were no significant trends in any safety parameter. D-4F was detectable in plasma at all doses with a Tmax of 30 min, 1 hr, and 2 hr for 30, 100, and 300 mg, respectively. The AUC(0-t) was 27.81 ng*hr/mL and 54.71 ng*hr/mL for the 300 and 500 mg dose groups, respectively and 17.96 ng*hr/mL for the 500 mg dose given with food. The HDL anti-inflammatory index significantly improved at 4 hours at the 300 mg dose and 2 hr at the 500 mg dose compared to placebo (p<0.05). There were no changes in plasma lipid or lipoprotein levels. We conclude that unformulated D-4F has low bioavailability that is improved under fasting conditions, and that a single dose of D-4F is safe and well tolerated, and may improve the HDL anti-inflammatory index.
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