Pharmacology Immediate release niacin-aspirin prodrug low density lipoprotein cholesterol Apolipoprotein B Triglycerides thromboxane prostaglandin
Mark T. Ledwidge, Fiona Ryan, David M Kerins, Damian O Connell, Gene Cafali, Shona Harmon, Michael Jones, John F Gilmer, In-vivo impact of prodrug isosorbide-5-nicotinate-2-aspirinate on lipids and prostaglandin D2: is this a new immediate-release therapeutic option for niacin?, Atherosclerosis, 2012
To evaluate the pharmacokinetics and effects of the first immediate-release (IR) niacin-aspirin prodrug (ST0702) on lipid, prostaglandin and thromboxane levels in non-human primates (NHPs).
We compared 28 mg/kg crystalline IR niacin, equimolar doses of crystalline IR ST0702 and control (daily oral gavage) on low density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) and triglycerides (Tg) in NHPs (6 per group) over 48 hours. In addition, we compared IR niacin and ST0702 effects on prostaglandin (PG)D2, ex-vivo thromboxane B2 (TXB2) levels and plasma pharmacokinetics.
ST0702 is metabolised in-vivo to aspirin, niacin and salicylic acid with Tmax values of 30, 45 and 95 minutes respectively using a non-compartmental model. ST0702 resulted in 38% and 40% reductions in LDL-C and ApoB levels compared to control over the 48 hour period (p = 0.027 and p = 0.012 respectively). Corresponding values were 32% and 25% for niacin (both p = NS vs control). ST0702, but not niacin, decreased Tg levels (p = 0.017 for between group difference). Post prandial glycaemia was attenuated vs baseline in the ST0702 group only. Ex-vivo serum TXB2 generation was suppressed at 15 minutes and complete suppression of TXB2 was sustained at 24 hours (p < 0.01 vs niacin). ST0702 suppressed PGD2 exposure eightfold (p = 0.012) compared to niacin over the first 24 hours
This two-dose study in NHPs suggests that ST0702 is more effective than IR niacin on lipid profiles, while suppressing TXB2 and PGD2 increases and preventing post-prandial glycaemia. ST0702 shows promise as a new IR therapeutic option for niacin
Please note: There is a known bug in some browsers that causes an
error when a user tries to view large pdf file within the browser window.
If you receive the message "The file is damaged and could not be
repaired", please try one of the solutions linked below based on the
browser you are using.
Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.