Increased levels of plasma high-density lipoprotein (HDL) cholesterol have been described after exposure to different dietary (such as ethanol) and environmental (such as chlorinated pesticides) factors as well as intense physical training. Several lipid-lowering drugs have also been shown to elevate HDL cholesterol. These findings are of particular interest, because adult levels of the putatively protective lipoprotein fraction appear not to be regulated by genetic factors. Four hypolipidemic drugs are herein considered, all of which reportedly elevate HDL cholesterolemia. Two of them, bezafibrate and fenofibrate, belong to the class of "fibrate" derivatives; nicotinic acid (NA) and etofibrate (E) show some similarities, E being the chemical association between nicotinic acid and clofibrate. In most studies, bezafibrate (B), with a very short half-life (2.1 hours), has induced an HDL cholesterol elevation of about 20%, both in types II and IV hyperlipidemic patients; it is controversial whether HDL2 rather than HDL3 levels are elevated by B. Fenofibrate (F) shows prolonged plasma half-life in man (>21 hours) and markedly increases HDL cholesterol levels, particularly in type IV patients; data are less homogeneous in type IIA and IIB cohorts. It appears that F may increase apoprotein C-II levels in very low density lipoproteins, possibly an index of stimulated lipoprotein lipase activity. Both B and F may behave as "catabolic agents," stimulating the breakdown of triglyceride-rich lipoproteins and the transfer of surface components (free cholesterol) to HDL. A different case may be that of NA, which prevents the decrease of HDL cholesterol induced by carbohydrate-rich diets in volunteers. NA reduces the catabolism of HDL and markedly increases (300% or more) the HDL2 HDL3 ratio in both volunteers and type IV patients, but not in type IIB patients. Whether, in addition to a "sparing" action on HDL, NA may also increase HDL levels by stimulating lipoprotein lipase activity is being disrupted. Finally, E may increase HDL cholesterol by 10% or more while exerting significant hypocholesterolemic activity. This compound is of interest because it may stimulate the release of prostacyclin from the arterial wall; prostacyclin may be derived from HDL phospholipids, unusually rich in arachidonic acid. This observation may offer another clue to the understanding of the mode of arterial protection exerted by HDL.

Influence of bezafibrate, fenofibrate, nicotinic acid and etofibrate on plasma high-density lipoprotein levels / R. Paoletti, G. Franceschini, C. R. Sirtori. - In: THE AMERICAN JOURNAL OF CARDIOLOGY. - ISSN 0002-9149. - 52:4(1983), pp. 21B-27B.

Influence of bezafibrate, fenofibrate, nicotinic acid and etofibrate on plasma high-density lipoprotein levels

R. Paoletti
Primo
;
G. Franceschini
Secondo
;
C. R. Sirtori
Ultimo
1983

Abstract

Increased levels of plasma high-density lipoprotein (HDL) cholesterol have been described after exposure to different dietary (such as ethanol) and environmental (such as chlorinated pesticides) factors as well as intense physical training. Several lipid-lowering drugs have also been shown to elevate HDL cholesterol. These findings are of particular interest, because adult levels of the putatively protective lipoprotein fraction appear not to be regulated by genetic factors. Four hypolipidemic drugs are herein considered, all of which reportedly elevate HDL cholesterolemia. Two of them, bezafibrate and fenofibrate, belong to the class of "fibrate" derivatives; nicotinic acid (NA) and etofibrate (E) show some similarities, E being the chemical association between nicotinic acid and clofibrate. In most studies, bezafibrate (B), with a very short half-life (2.1 hours), has induced an HDL cholesterol elevation of about 20%, both in types II and IV hyperlipidemic patients; it is controversial whether HDL2 rather than HDL3 levels are elevated by B. Fenofibrate (F) shows prolonged plasma half-life in man (>21 hours) and markedly increases HDL cholesterol levels, particularly in type IV patients; data are less homogeneous in type IIA and IIB cohorts. It appears that F may increase apoprotein C-II levels in very low density lipoproteins, possibly an index of stimulated lipoprotein lipase activity. Both B and F may behave as "catabolic agents," stimulating the breakdown of triglyceride-rich lipoproteins and the transfer of surface components (free cholesterol) to HDL. A different case may be that of NA, which prevents the decrease of HDL cholesterol induced by carbohydrate-rich diets in volunteers. NA reduces the catabolism of HDL and markedly increases (300% or more) the HDL2 HDL3 ratio in both volunteers and type IV patients, but not in type IIB patients. Whether, in addition to a "sparing" action on HDL, NA may also increase HDL levels by stimulating lipoprotein lipase activity is being disrupted. Finally, E may increase HDL cholesterol by 10% or more while exerting significant hypocholesterolemic activity. This compound is of interest because it may stimulate the release of prostacyclin from the arterial wall; prostacyclin may be derived from HDL phospholipids, unusually rich in arachidonic acid. This observation may offer another clue to the understanding of the mode of arterial protection exerted by HDL.
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/182429
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