Endpoints In Drug Development Research Articles

Use of Apolipoprotein Parameters and Endpoints in Drug Development and Approval Processes

Plasma lipoproteins are particles containing lipid and protein moieties. The major constituents of lipid moieties include cholesterol, cholesteryl esters, triglycerides, and phospholipids. Protein moieties include proteins referred to as apolipoproteins (apo) AI, A-II, A-IV, B-100, C-I, C-II, C-III, D, E, F, G, I, and J.1 It is now generally accepted that apolipoproteins play essential roles in maintaining the structural integrity and functional specificity of plasma lipoproteins.1–3 Apolipoproteins are directly involved in metabolic conversions of different lipoprotein classes including secretion, prevention of premature removal from the circulation, recognition of binding and removal sites on cellular surfaces, and activation of lipolytic enzymes. Because of these properties, apolipoprotein concentrations may be used as valuable clues for identifying normal and impaired processes of lipid transport.3–6 However, despite the undisputed significance of apolipoproteins for the formation and lipid-transport capacity of lipoproteins, the pathophysiologic processes of lipid transport and corresponding interventions have usually been characterized, defined, and monitored by lipid, not apolipoprotein, concentrations. This attitude has resulted from various factors: historical development of the field, conceptual views about lipid transport and atherogenesis, and methodologic considerations. Thus, the National Cholesterol Education Program (NCEP) has provided recommendations for the desirable concentrations and reliable measurement of lipids, but not apolipoproteins.7,8