This Figure shows the results of a stable isotope study to map the effects of torcetrapib on apolipoprotein metabolism. There is some increase in apoB100 clearance, but minimal effects on apoB48 clearance, although there is a reduction in the synthesis of apoB48; there is a decline in the fractional catabolic rate of apoA-I of about 7%, which is not striking. The major effect here is markedly increasing the amount of cholesterol ester in the HDL particle.
This suggests that it remains to be determined whether the CETP inhibitors will be beneficial. The difficulty is that the CETP inhibitors can bind to the transfer protein and to the HDL particle, thus forming a complex between the drug, HDL, and the transfer protein; that complex may not be very physiologic and it may interfere with the normal physiology of reverse cholesterol transport.
J Clin Lipidol. 2011; 5(6).