The Pharmaceutical Journal
Vol 268 No 7196 p597-604
4 May 2002

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Circulation (www.circ.ahajournals.org)

Plasma protein inhibitor raises HDL

Use of a cholesteryl ester transfer protein inhibitor, JTT-705, in humans is an effective way to raise high-density lipoprotein (HDL) levels, a new study shows.

Dr Greetje de Grooth, University of Amsterdam, and colleagues explain that cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins and that high plasma levels of CETP are associated with low HDL levels.

They evaluated the safety and efficacy of JTT-705 in 198 healthy subjects with hyperlipidaemia. Subjects were randomly assigned to receive one of three doses of JTT-705 (300mg, 600mg, 900mg) or placebo, daily for four weeks.

The researchers say that a dose-dependent decrease in CETP activity was observed after one week of treatment. Four weeks of treatment with a 900mg dose of JTT-705 resulted in a 37.2 per cent decrease in CETP activity, a 34 per cent increase in HDL (P<0.0001 for both) and a 7 per cent decrease in low-density lipoprotein (P=0.017). Phospholipid transfer protein and lecitin-cholesterol acyltransferase were unaffected, underlining the specificity of the drug, they say. Doses of up to 900mg were well tolerated but can have mild gastrointestinal effects.

However, the researchers comment that further studies are needed to investigate whether the observed increase in HDL translates into a corresponding reduction in the risk of coronary artery disease.

The study is published in Circulation (2002;105:2159).