acipimox and Hypercholesterolemia

Thirty patients were investigated with hyperlipoproteinaemia, 15 patients with non-insulin dependent diabetes mellitus (NIDDM) and 15 with primary hyperlipoproteinaemia. The patients took 250 mg acipimox (5-metyl-pyrazine-carboxylic acid 4-oxide) 3 times per day for 2 months. Serum examinations were performed before and after 1 and 2 months of acipimox administration. After treatment the cholesterol and triglyceride levels decreased in both groups. Patients with NIDDM had 11% increase of high density lipoprotein-cholesterol (HDL-C) level at the end of the first, and 18% increase at the end of the second month, while patients with primary hyperlipoproteinaemia did not change significantly. The low density lipoprotein (LDL) level did not change significantly in either groups of patients. The apolipoprotein A 1 (apo A 1) levels increased significantly during the second month of acipimox administration. Uric acid levels decreased in both groups, but significant change could be detected mainly in the NIDDM group. Serum glucose level did not change in the non-diabetic patients, while it decreased significantly in the NIDDM group.

Topics: Apolipoprotein A-I; Blood Glucose; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemias; Hypertriglyceridemia; Hypolipidemic Agents; Lipoproteins, LDL; Male; Middle Aged; Pyrazines; Time Factors; Triglycerides; Uric Acid

Topics: Humans; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Hypolipidemic Agents; Pyrazines

The effects of combined therapy with acipimox (1250 mg/day) and cholestyramine (20 g/day) were examined in a group of 7 subjects with primary moderate hypercholesterolaemia (total cholesterol >=7 mmol/L). Radiolabeled VLDL subfraction turnovers were performed at baseline, during acipimox therapy and during combined therapy. Acipimox and combined therapies lowered plasma low density lipoprotein (LDL)-cholesterol by 20% (P<0.001) and 27% (P<0.001) respectively. The marked fall in LDL-cholesterol associated with acipimox therapy, was due to a reduced production rate of LDL (apolipoprotein) apoB. This is shown to be a result of reduced direct LDL apoB production, reduced IDL to LDL transfer consistent with inhibition of hepatic triglyceride lipase, and with a reduction in the overall throughput of VLDL1 apoB. With combined therapy both reduced production and increased catabolism of apoB containing LDL precursors and of LDL itself have to be invoked to explain the fall in plasma LDL-cholesterol.

Topics: Adult; Apolipoproteins B; Cholestyramine Resin; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipoproteins, VLDL; Male; Middle Aged; Pyrazines

Topics: Adult; Aged; Cholesterol; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Pyrazines

Topics: Administration, Oral; Bezafibrate; Bilirubin; Colestipol; Gilbert Disease; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipids; Liver; Liver Function Tests; Lovastatin; Male; Middle Aged; Pravastatin; Pyrazines; Simvastatin

Two independent studies were designed to investigate the separate and combined effects of acipimox and cholestyramine on plasma low density lipoprotein subfractions. In the first study, normolipidaemic subjects were given cholestyramine (16 g day-1, 4 weeks), followed, after an 8-week wash-out period, by acipimox (750mg day-1, 4 weeks). In the second study, moderately hypercholesterolaemic subjects were prescribed acipimox (1250mg day-1, 10 weeks), followed by acipimox in combination with low dose cholestyramine (12g day-1) for a further 10 weeks. In the normal subjects, cholestyramine decreased total LDL mass (density (d) = 1.019-1.063g ml-1) by selectively reducing the largest, least dense LDL-I (d 1.025-1.034 g ml-1, P less than 0.05) and LDL-II (d 1.034-1.044 g ml-1, P less than 0.005) subfractions. The small, dense LDL-III (d 1.044-1060 g ml-1) showed a variable response to the resin. In the same subjects acipimox produced no overall change in total LDL mass but showed a tendency to redistribute LDL towards LDL-I (+10%) and LDL-II (+10%) in a manner related to the changes in plasma triglyceride (TG) (TG vs. LDL-III r = 0.75, P less than 0.05). In the hypercholesterolaemic subjects acipimox induced a substantial redistribution of LDL subfractions (LDL-I +84% P less than 0.05; LDL-III -50%) without affecting total LDL mass. The addition of cholestyramine produced a significant decrease in total LDL mass which was again confined to the LDL-I (-28%) and LDL-II (-23%) subfractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Centrifugation, Density Gradient; Cholestyramine Resin; Drug Therapy, Combination; Electrophoresis; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipoproteins, LDL; Male; Middle Aged; Pyrazines; Reference Values