Plasma triglyceride, effect

Pioglitazone decreases plasma triglycerides by 10% to 20%, whereas rosiglitazone tends to have no effect. Pioglitazone does not cause significant increases in LDL cholesterol, whereas LDL cholesterol may increase by 5% to 15% with rosiglitazone. 

Several clinical studies revealed that administration of fenofibrate produces reductions in total-C, LDL-C, apo B, total triglycerides, and triglyceride-rich (very low density) lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in HDL-C, apo AI, and apo AIL However, since fenofibrate is rapidly converted to fenofibric acid during absorption and fenofibric acid, but not fenofibrate, is found circulating in plasma, the effects of fenofibric acid have been extensively evaluated in these studies. 

Mechanism of Action An antihyperlipidemic that inhibits hydroxymethylglutaryl-CoA (HMG CoA) reductase, the enzyme that catalyzes the early step in cholesterol synthesis. Therapeutic Effect Decreases LDL and VLDL cholesterol, and plasma triglyceride levels increases HDL cholesterol concentration. 

Mechanism of Action An antihyperlipidemic that enhances synthesis of lipoprotein lipase and reduces triglyceride-rich lipoproteins and VLDLs. Therapeutic Effect Increases VLDL catabolism and reduces total plasma triglyceride levels. Pharmacokinetics Well absorbed from the GI tract. Absorption increased when given with food. Protein binding 99%. Rapidly metabolized in the liver to active metabolite. Excreted primarily in urine lesser amount in feces. Not removed by hemodialysis. Half-life 20 hr. 

Mechanism of Action An HMG-CoA reductase inhibitor that interferes with cholesterol biosynthesis by preventing the conversion of HMG-CoA reductase to meva-lonate, a precursor to cholesteroh Therapeutic Effect Lowers serum LDL and VLDL cholesterol and plasma triglyceride levels increases serum HDL concentration. Pharmacokinetics Poorly absorbed from the G1 tract. Protein binding 50%. Metabolized in the liver (minimal active metabolites). Primarily excreted in feces via the biliary system. Not removed by hemodialysis. Half-life 2.7 hr. 

Mechanism of Action An antihyperlipidemicthat interferes with cholesterol biosynthesis by inhibiting the conversion of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate, a precursor to cholesterol. Therapeutic Effect Decreases LDL cholesterol, VLDL, and plasma triglyceride levels, increases HDL concentration. Pharmacokinetics Protein binding 88%. Minimal hepatic metabolism. Primarily eliminated in the feces. Half-life 19 hr (increased in patients with severe renal dysfunction). 

Gemfibrozil reduces plasma triglycerides by 40 to 55% by decreasing the concentration of VLDL. Its effectiveness is less in lowering LDL. 

The effect of di(2-ethylhexyl) phthalate in diet (2% for 21 days) on lipoprotein metabolism in male Wistar rats was evaluated (Mocchiutti Bernal, 1997). The observed reduction in plasma triglyceride levels was associated with (and attributed to) increased activity of extrahepatic lipoprotein lipase. 

The effects of di(2-ethylhexyl) adipate (1% of diet) on plasma lipids were evaluated in male Upjohn TUC (SD) rats (Bell, 1984). After two weeks and four weeks (but not seven weeks) of feeding, plasma cholesterol levels were significantly decreased. After four weeks (but not two or seven weeks) of feeding, plasma triglyceride levels were significantly decreased. Hepatic cholesterol s mthesis was diminished by di(2-ethylhexyl) adipate consumption (Bell, 1983, 1984). 

Bhathena, S.J., Ali, A.A., Mohamed, A.I., Hansen, C.T., and Velasquez, M.T. 2002. Diffemtial effects of dietary flaxseed protein and soy protein on plasma triglyceride and uric acid levels in animal models. J. Nutr. Biochem. 13, 684-689. 

However, the reductase inhibitors clearly induce an increase in high-affinity LDL receptors. This effect increases both the fractional catabolic rate of LDL and the liver s extraction of LDL precursors (VLDL remnants), thus reducing plasma LDL (Figure 35-2). Because of marked first-pass hepatic extraction, the major effect is on liver. Preferential activity in liver of some congeners appears to be attributable to tissue-specific differences in uptake. Limited reduction of LDL levels in patients who lack functional LDL receptors indicates that decreases in de novo cholesterologenesis also contribute to cholesterol reduction. Modest decreases in plasma triglycerides and small increases in HDL also occur. 

Hockey KJ, Anderson RA, Cook VR, Hantgan RR, Weinberg RB. Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance. J Lipid Res. 2001, 42 211-217. 

The effect of oral barium exposure on various blood chemistry parameters that are important for cardiovascular function has been evaluated in only one experimental study with humans (Wones et al. 1990). In this study, 0.2 mg barium/kg/day as barium chloride was supplied in the drinking water of subjects for 4 weeks. No clinically significant changes were noted in any of the blood chemistry parameters monitored (total plasma cholesterol plasma triglycerides plasma HDL and LDL cholesterol plasma apolipoproteins and serum glucose, potassium, calcium, and albumin). 

Pullen, D.L., Palmquist, D.L., Emery, R.S. 1989. Effect of days of lactation and methionine hydroxy analog on incorporation of plasma fatty acids into plasma triglycerides.. / Dairy Sci. 72, 49-58. 

In the early 1990s, a series of well-designed clinical studies convincingly demonstrated that TFAs increased plasma total and LDL-cholesterol to levels similar to those produced by saturated fatty acids. More than this, TFAs reduced plasma HDL-cholesterol level. The overall effect was that the ratio of LDL-cholesterol to HDL-cholesterol was approximately double that for an equivalent intake of saturated fatty acids (Ascherio et al., 1999). In addition, TFAs adversely affect other CHD risk factors. Plasma triglycerides and Lp[a] levels are increased (Ascherio et al., 1999) and it was shown recently that consumption of TFAs was associated with a deleterious increase in small, dense LDL particles (Mauger et al., 2003). 

Increase in LDL levels no effect on HDL, VLDL or plasma triglyceride levels significant cause of hypercholesterolemia and premature coronary artery disease Decreased levels of plasma cholesteryl esters and lysolecithin abnormal LDLs (Lp-X) and VLDLs symptoms also found associated with cholestasis... 

TABLE 6.7 Effect of Eating on Plasma Triglycerides and ApoEpoprotein E... 

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