PMIDOWN STATDA DCOMLR IS IS VI DP TI PG AB They

8497455
NLM
MEDLINE
19930622
19930622
20131121
0032-5473 (Print)
0032-5473 (Linking)
69 Suppl 1
1993
Mechanism of action of fibrates.
S34-41
Fibrates are effective in hypertriglyceridaemia and hypercholesterolaemia.
affect both triglyceride-rich and cholesterol-rich particles and have at l

east
four separate modes of action. These include limitation of substrate avail
ability
for triglyceride synthesis in the liver; promotion of the action of lipopr
otein
lipase; modulation of low density lipoprotein (LDL) receptor/ligand intera
ction
and stimulation of reverse cholesterol transport. Studies of LDL metabolis
m
suggest the existence of two separate catabolic pathways involving the LDL
receptor and scavenger mechanism(s). The former route is anti-atherogenic;
the
latter pro-atherogenic. At low triglyceride levels, the fractional clearan
ce of
LDL by the receptor is high. The action of fibrates is to promote the secr
etion
of LDL which is cleared by a receptor-mediated mechanism. Catabolism of th
is
fraction increases from 40% of the plasma pool per day in untreated to 60%
per
day in treated subjects. By activating lipoprotein lipase, fibrates also r
educe
the amount of small dense LDL, the fraction which is most likely to genera
te
peroxidation products. Hence, fibrates stimulate LDL receptor-dependent cl
earance
mechanisms and reduce the amount of LDL available for oxidation.
FAU - Shepherd, J
AU - Shepherd J
AD - Institute of Biochemistry, Royal Infirmary, Glasgow.
LA - eng
PT - Journal Article
PT - Review
PL - ENGLAND
TA - Postgrad Med J
JT - Postgraduate medical journal
JID - 0234135
RN - 0 (Apolipoproteins B)
RN - 0 (Fibric Acids)
RN - 0 (Hypolipidemic Agents)
RN - 0 (Lipoproteins, LDL)
RN - 0 (Receptors, LDL)
RN - 53PF01Q249 (Clofibric Acid)
RN - F8252JGO9S (ciprofibrate)

RN RN RN SB MH MH MH MH MH MH MH MH MH MH MH MH MH MH RF EDATMHDACRDTPST SO -

Q8X02027X3 (Gemfibrozil)
U202363UOS (Fenofibrate)
Y9449Q51XH (Bezafibrate)
IM
Apolipoproteins B/drug effects
Bezafibrate/pharmacology
Clofibric Acid/analogs & derivatives/pharmacology
Female
Fenofibrate/pharmacology
Fibric Acids
Gemfibrozil/pharmacology
Humans
Hypercholesterolemia/blood
Hypertriglyceridemia/blood
Hypolipidemic Agents/*pharmacology
Lipoproteins, LDL/blood/drug effects
Male
Receptors, LDL/drug effects
11
1993/01/01
1993/01/01 00:01
1993/01/01 00:00
ppublish
Postgrad Med J. 1993;69 Suppl 1:S34-41.