Integration of New and Classical Techniques in Drug Development. PET Application to Propionyl-L-Carnitine Pharmacokinetic Study

Abstract

Propionyl-L-carnitine (PLC) is an Acyl derivative of L-carnitine and is a physiological constituent normally found in the body. PLC presents some advantages over L-carnitine in the treatment of patients with heart failure, angina and peripheral vascular disease, due to its peculiar biochemical activity. Infact, PLC shows a better transport pathway into the cells than L-carnitine (LC), moreover it represents the possibility for Propionate to enter in an activated form into the cell, thus not requiring energy to undergo its biochemical transformation. “The biochemical rationale for PLC administration concerns the possibility of feeding the tricarboxylic acid cycle (anaplerosis) with the carbon skeleton of propionate, without altering the energy metabolism”, (Di Lisa et al). This latter point is very important, because it can explain the opposite effect of PLC and Propionate per se; as a matter of fact PLC showed a protective effect on ischemic heart, while exposure to Propionate led to an impairment of ischemic damage. “Thus the peculiar beneficial effect of PLC can arise from the anaplerotic mechanism occurring in the presence of optimal concentrations of ATP, L-carnitine and CoA”, (Di Lisa et al).