Effect Of Cholestyramine Research Articles

Effect of Cholestyramine on the Pharmacokinetics and Pharmacodynamics of Bezafibrate in Rats.

The interaction between bezafibrate (BF) and cholestyramine (CT), an anionic exchange resin, was evaluated both in vitro and in vivo.In an in vitro study, the incubation of 100 or 1000 μg/ml of BF solution with 200 mg of CT at various pH (2.0, 5.0 and 7.0) solutions was performed at 37° for 10 min in order to evaluate the binding ability of BF to CT. After incubation, 100 μg/ml of BF bound to CT by 85.41, 89.40 and 92.14% at pH 2, 5 and 7, respectively, and 1000 μg/m1 of BF bound to CT by 66.28 and 69.02%, at pH 5 and 7, respectively.Next, the effect of CT on the pharmacokinetics and pharmacodynamics of BF was examined in experimentally induced hypercholesterolemic rats. When BF (50 mg/kg/day p. o.) and CT (600 mg/kg/day p.o.) were continuously administered to rats once a day for 7 days, CT caused a significant reduction in the cholesterol-lowering effect of BF in accordance with a significant decrease in the plasma level of BF, compared with the administration of BF alone. The decreased plasma BF level closely reflected the cholesterol-lowering effect of BF. Even when CT was given 3h after BF, the pharmacokinetics and pharmacodynamics of BF were not sufficient to achieve a full recovery of the BF level. The present observations thus suggest that CT should be used with extreme caution in patients receiving BF.

Cholestyramine Influences Meal-Stimulated Pancreaticobiliary Function and Plasma Cholecystokinin Independent of Gastric Emptying and Food Digestion

Background: Cholestyramine enhances gallbladder emptying and plasma cholecystokinin responses to oral ingestion of a mixed meal. It is not known whether this effect occurs independently of alterations in gastric emptying or maldigestion of nutrients. Methods: We perfused 15 g of an amino acid meal intraduodenally for 60min in seven healthy volunteers, once with and once without cholestyramine. Intraduodenal perfusion of saline with or without cholestyramine (6 g/h) was started 60 min before the amino acid meal and continued for 2 h. Results: Cholestyramine markedly enhanced the incremental plasma cholecystokinin response to the meal from 36 ±12 to 139 ± 25 pmol/1 60 min (P < 0.005), incremental amylase output from 2.4 ± 0.7 to 5.7 ± 0.7 kU/h (P < 0.05), and incremental integrated gallbladder contraction from1948 ± 235 to 2840 ± 189% 60 min (P < 0.05). Conclusion: The enhancing effect of cholestyramine on postprandial gallbladder contraction, pancreatic enzyme secretion, and plasma cholecystokinin release is not dependent on gastric emptying rates or appropriate digestion of nutrients.

Sitosterolemia: opposing effects of cholestyramine and lovastatin on plasma sterol levels in a homozygous girl and her heterozygous father

Sitosterolemia is a genetic disorder characterized by sitosterol accumulation in plasma and clinically accelerated atherosclerosis. Under a condition of metabolic control with a 30% fat, low-sitosterol diet, we compared the effects of monotherapy and dual-drug treatment with lovastatin and cholestyramine on plasma sterol parameters and endogenous cholesterol synthesis in a homozygous sitosterolemic patient with concomitant heterozygous familial hypercholesterolemia (FH), her obligate heterozygous father, and hyperlipidemic control subjects. We found that for both the sitosterolemic homozygote and heterozygote, cholestyramine plus lovastatin dual therapy proved not to be superior to either drug treatment alone. In the homozygous patient, cholestyramine accounted for the decrease of plasma sterol (ie, lovastatin was ineffective), whereas in the heterozygote, lovastatin represented the margin of difference (ie, low-dose cholestyramine was relatively ineffective). Thus, the best treatment option for this homozygote child and her heterozygote father appears to be monotherapy with cholestyramine and lovastatin, respectively. Stimulation by bile acid malabsorption produced a dramatic decrease of plasma sterols in the homozygote, without increasing endogenous cholesterol synthesis, but this therapy was ineffective in the heterozygote. Decreasing endogenous cholesterol synthesis with lovastatin was effective in the heterozygote, but ineffective in the homozygote. In suspected sitosterolemia, a poor sterol response to lovastatin and a dramatic response to cholestyramine may differentiate homozygous from heterozygous and other familial forms of hyperlipidemia.

P-791 - Effects of cholestyramine on hepatic drug-metabolizing enzyme activities and lipids levels in spontaneously hyperlipidemic rats

P-791 - Effects of cholestyramine on hepatic drug-metabolizing enzyme activities and lipids levels in spontaneously hyperlipidemic rats

The effects of simvastatin and cholestyramine, alone and in combination, on hepatic cholesterol metabolism in the male rat

The influence of dietary simvastatin, cholestyramine, and the combination of simvastatin plus cholestyramine on hepatic cholesterol metabolism has been investigated in male rats. Recovery from the effects of the drugs was also investigated by refeeding normal chow for 24 h. Both drugs, alone and in combination, increased 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity in vitro, but activity returned toward control values, after drug withdrawal. Acyl-CoA:cholesterol acyltransferase (ACAT) was significantly reduced (P < 0.001) by simvastain (-75%), cholestyramine (-71%), and by the drug combination (-81%), due both to a decrease in microsomal cholesterol and to nonsubstrate-dependent modulation of enzyme activity. Refeeding control diet increased ACAT activity but not to control levels. The enhanced activity arose partly from higher microsomal cholesterol and partly from increases in total enzyme activity. Cytosolic neutral cholesteryl ester hydrolase (CEH) activity was substantially elevated by simvastatin (3-fold) and by the drug combination (6-fold), whereas the effect of cholestyramine was smaller (1.5-fold). Normal chow for 24 h only partially returned cytosolic CEH activity to control values. Microsomal CEH activity was increased by simvastatin, alone and in combination with cholestyramine (1.4 to 1.7-fold), and was also enhanced, in the cholestyramine-treated animals, following drug withdrawal. Removal of simvastatin did not allow recovery of this enzyme activity, while withdrawal of the drug combination led to values 29% below controls. The results indicate that in the rat, simvastatin and cholestyramine alter both ACAT and CEH activity, as well as inhibiting HMG-CoA reductase activity.

Cholestyramine alters the lipid and energy metabolism of chicks fed dietary medium‐or long‐chain triacylglycerol

The effects of cholestyramine, a bile acid binding polymer, on the lipid and energy metabolism of chicks given dietary medium-chain triacylglycerol (MCT) or long-chain triacylglycerol (LCT) were investigated. Chicks (from 8 to 17 days of age) were fed diets containing MCT or LCT at 200 g oil/kg diet with or without 2% cholestyramine under equalized feeding conditions. An adjusted LCT diet was formulated in order to supply another group with daily nutrients and dietary metabolizable energy (ME) equal to MCT groups, except for corn starch. ME intakes of chicks given MCT or LCT diets were reduced by cholestyramine; consequently, fat and energy retention was reduced, though the reduction was more drastic in chicks fed LCT. This was caused by a change in amounts of the fecal excretion of fat and bile acids. Cholestyramine enhanced the excretion of octanoic acid (8:0) in the feces, which suggests that bile acids are needed for 8:0 absorption. Cholestyramine affects the utilization of dietary MCT and LCT by lowering fat and energy retention in chicks. However, the effect of cholestyramine on MCT utilization was smaller than its effect on utilization of LCT.

Effect of cholestyramine on pancreatic enzyme secretion, gallbladder motility and plasma cholecystokinin release in response to an intraduodenal amino acid meal: [formula omitted], A. Loualidi, W.P.M. Hopman, G. Rosenbusch 1, J.L. Willems 2 and J.B.M.J. Jansen. Depts. of Gastroenterology, Radiology 1 and Clinical Chemistry 2, University Hospital Nijmegen, The Netherlands

Effect of cholestyramine on pancreatic enzyme secretion, gallbladder motility and plasma cholecystokinin release in response to an intraduodenal amino acid meal: [formula omitted], A. Loualidi, W.P.M. Hopman, G. Rosenbusch 1, J.L. Willems 2 and J.B.M.J. Jansen. Depts. of Gastroenterology, Radiology 1 and Clinical Chemistry 2, University Hospital Nijmegen, The Netherlands

Effectiveness of cholestyramine in the detoxification of zearalenone as determined in mice.

Effectiveness of cholestyramine in the detoxification of zearalenone as determined in mice.

Comparison of Pravastatin Alone and with Cholestyramine in the Treatment of Hypercholesterolemia.

To compare the efficacy and safety of pravastatin alone and a combination of it and cholestyramine in low doses for the treatment of primary hypercholesterolemia, we conducted a randomized, parallel group study. A total of 30 patients with a mean age of 55 years were enrolled in the study. They were randomized into two groups. One group (n=15) received pravastatin (20 mg/day) while the other group (n=15) received pravastatin (10 mg/day) plus cholestyramine (8 g/day) for 24 weeks. At 12 weeks, results showed that pravastatin alone led to a 21% reduction in total plasma cholesterol and a 24% reduction in low-density lipoprotein (LDL) cholesterol concentrations. There was no significant change in high-density lipoprotein cholesterol and total triglyceride concentrations. In the pravastatin-cholestyramine group, there was similar reduction in total cholesterol concentration (24%). However, the reduction in the LDL cholesterol concentration was higher (32%) ; and the plasma triglyceride concentration was increased by 13%. No significant side effects occurred in either group during the study period. Similar results were observed at 24 weeks. In conclusion, pravastatin was demonstrated to be an effective, well-tolerated drug for treating hypercholesterolemia. A low dose combination of pravastatin and cholestyramine was significantly more effective than pravastatin alone in higher doses in terms of LDL cholesterol reduction. By use of a lower dose of cholestyramine, the side effects of cholestyramine are much reduced and the patient's compliance is improved.

Decreased plasma concentrations of imipramine and desipramine following cholestyramine intake in depressed patients.

The effect of cholestyramine (4 g t.i.d. for 5 days) on the steady-state plasma concentrations of imipramine and desipramine was assessed in six depressed patients receiving chronic treatment with imipramine (75-150 mg/day). Compared with baseline, cholestyramine treatment was associated with an average 23% decrease in plasma imipramine levels [from 211 +/- 95 to 159 +/- 67 nmol/L, (mean +/- SD), p < 0.05], whereas desipramine levels decreased only marginally. These data suggest that administration of cholestyramine at therapeutic doses impairs the gastrointestinal absorption of concurrently prescribed imipramine by an extent that is potentially clinically significant.

Cholesterol synthesis and esterification in isolated enterocytes: Regulation by cholesterol and cholestyramine feeding

The purpose of the present study was to investigate the physiological control of the main regulatory enzymes of cholesterol metabolism in isolated enterocytes obtained from chick duodenum, jejunum and ileum. Cholesterol feeding resulted in an inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase and mevalonate 5-pyrophosphate decarboxylase, while cholestyramine feeding increased reductase activity in all the regions studied and decarboxylase activity only in duodenum. Cholesterol feeding markedly increased acyl-CoA:cholesterol acyltransferase, but the effects of cholestyramine were less clear. The effects on transferase activity cannot be due to differences in the availability of acyl-CoA as exogenous substrate as no significant differences were found in acyl-CoA hydrolase activity after any of the dietary treatments. The effects of cholesterol feeding were related to changes in the cholesterol content of epithelial cells, whereas in the case of cholestyramine this relationship was less apparent.

Hypocholesterolemic effects of cholestyramine and colestipol in patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB have been heterozygous for this disorder and their plasma contains both normal and defective-binding LDL particles, with a predominance of the latter. In the present report, we have compared the hypocholesterolemic effects of bile acid sequestrant therapy (cholestyramine or colestipol) in eight patients with FDB, to the response seen in sixteen patients with heterozygous familial hypercholesterolemia (FH), treated with the same drugs. Concentrations of LDL cholesterol fell by 32.0% in the patients with FDB and by 21.6% in the patients with FH. The results indicate that the hypercholesterolemia of both FDB and FH responds to treatment with bile acid sequestrants.

Effects of cholestyramine and acipimox on subfractions of plasma low density lipoprotein. Studies in normolipidaemic and hypercholesterolaemic subjects.

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)

Effects of cholestyramine on lipoprotein levels and metabolism in Syrian hamsters

Oral administration of cholestyramine to adult male hamsters not only induced a marked decrease in plasma concentrations of cholesterol and LDL but had a similar lowering effect on plasma triacylglycerol and VLDL concentrations. The hypotriglyceridaemic effects of resin administration were not due to an increase in lipoprotein lipase, as post-heparin plasma lipoprotein lipase activities were unchanged, but rather to a 35% decrease in VLDL synthesis. Measurement of the disappearance rate of apolipoprotein B from VLDL after i.v. injection of 125I-labelled hamster or human VLDL into control and cholestyramine-fed recipient animals showed a 2-times lower T 1 2 in the drug-treated animals. The fraction of VLDL apolipoprotein B, recovered at any time after injection in the LDL, was equal or higher in cholestyramine-fed animals as compared to controls. These data indicate that the lowering in plasma LDL by cholestyramine in male hamsters is due not only to LDL receptor up-regulation but also to a lower rate of VLDL synthesis. No indications were found for a decreased efficiency of VLDL to LDL conversion in cholestyramine-fed animals.

Response to cholesterol-lowering drugs in familial defective apolipoprotein B-100

The effect of cholestyramine and simvastatin, given separately or in combination, on serum lipid concentrations in 11 patients with heterozygous familial defective apolipoprotein B-100 was compared with that in 11 matched patients with heterozygous familial hypercholesterolaemia. In both groups of patients there was a substantial fall in serum lipid levels in response to treatment. There were no significant differences between the reductions in serum total or low-density lipoprotein cholesterol levels in the two groups.

The effect of cholestyramine and activated charcoal on glipizide absorption.

1. The interference of cholestyramine and activated charcoal with the absorption of glipizide was studied. 2. In a cross-over study comprising three phases, single doses of cholestyramine (8 g), activated charcoal (8 g) or water only were given to six healthy volunteers together with a single dose of glipizide. 3. The absorption of glipizide was moderately (29%, P less than 0.01) reduced by cholestyramine and greatly reduced (81%, P less than 0.01) by activated charcoal. 4. If cholestyramine and glipizide are used concomitantly, glipizide should be taken 1-2 h beforehand. In acute glipizide overdosage, activated charcoal can be used to reduce absorption.

Treatment of familial hypercholesterolaemia: a controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels

The efficacy and safety of a new, selective inhibitor of cholesterol synthesis, pravastatin, and the bile acid-binding resin, cholestyramine, were compared in a randomized, double-blind study of 120 patients with familial hypercholesterolaemia. After a run-in period of 8-10 weeks with assessment of dietary habits, the patients were treated with pravastatin + placebo, placebo + cholestyramine, or placebo alone. Active pravastatin therapy was initiated with 10 mg b.i.d. for 6 weeks, and was increased to 20 mg b.i.d. for the following 6 weeks. Cholestyramine was given at 24 g d-1, or the highest tolerable dose. After 6 weeks of therapy, serum total and LDL cholesterol levels were reduced by 17% and 21%, respectively, on pravastatin treatment, whereas the corresponding reductions with cholestyramine treatment were 24% and 30%, respectively. With an increased dose of pravastatin, serum and LDL cholesterol concentrations were reduced by 23% and 28%, respectively, after 12 weeks; the effect of cholestyramine was unchanged. HDL cholesterol levels increased in response to pravastatin, by 7% and 9% after 6 and 12 weeks, respectively. Concomitant changes in the concentrations of apolipoproteins B and AI were observed. Three patients discontinued the study because of side-effects: two subjects were treated with pravastatin and one was given placebo. The prevalence of side-effects (including laboratory abnormalities) was 35% for pravastatin, 30% for placebo, and 53% (significantly higher) for cholestyramine. We conclude that pravastatin, in a 40 mg daily dose, is as effective as cholestyramine in lowering LDL cholesterol in familial hypercholesterolaemia. Since the frequency of side-effects is higher with cholestyramine, pravastatin offers a promising alternative for the therapy of this genetic disease.

Effect of Cholestyramine on Activity of Gentamicin in Vitro

To the Editor.— A combination of oral gentamicin and the basic anion exchange resin, cholestyramine is effective in the treatment of infants who have severe diarrhea for 7 days.1 Both drugs decrease the severity of the diarrhea and there is a considerable, beneficial interaction between them.2 The mode of action is not known, but we postulated that gentamicin acts by eliminating the abnormal bacterial microflora in the small bowel and cholestyramine by binding toxins or deconjugated and dehydroxylated bile salts.2

Diurnal Variation of Hepatic Cholesterol 7α-Hydroxylase Activity and Effect of Cholestyramine on Its Activity in SHRSP

Diurnal Variation of Hepatic Cholesterol 7α-Hydroxylase Activity and Effect of Cholestyramine on Its Activity in SHRSP

Effect of cholestyramine in early weaning on later response of serum and fecal steroid levels and cholesterol 7.ALPHA.-hydroxylase activity to high-cholesterol diet in ExHC rats.

Male ExHC (exogenous hypercholesterolemic) rats were either prematurely weaned at 17 days of age or allowed to nurse until 35 days of age. The prematurely weaned rats were either fed a diet containing cholestyramine or cholestyramine-free diet until 35 days of age. Cholestyramine supplementation markedly increased fecal bile acid excretion and modified the composition. After giving a stock diet for 7 weeks, all rats received a cholesterol-enriched diet for 9 weeks. The serum cholesterol level in later time was not affected by early dietary manipulation. The activity of hepatic cholesterol 7 alpha-hydroxylase and fecal bile acid excretion at the end of the cholesterol challenge decreased in the cholestyramine-pretreated group, when compared to the normally weaned group. Fecal excretion and the ratio of the secondary (deoxycholic and lithocholic acids) to the primary (cholic and chenodeoxycholic acids) bile acids significantly decreased in the early cholestyramine-treated group. These results suggest that a modification of bile acid metabolism in early life may strongly influence the hepatic and possibly colonic bile acid metabolism in later life, when challenged with a high-cholesterol diet.