Effect of cholestyramine on the fecal excretion of intravenously administered cholesterol-4-14C and its degradation products in a hypercholesterolemic patient

Moore, Richard B.; Crane, Catherine A.; Frantz, Ivan D.

doi:10.1172/jci105857

Cited by 71 publications

(13 citation statements)

References 30 publications

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“…The rapid turnover of the primary trihydroxy bile acid, taurocholate (Table I), and the virtual disappearance of its dihydroxy metabolic product, deoxycholate (Table II A), during the administration of cholestyramine is in keeping with previous reports documenting increased fecal bile acid excretion and cholesterol turnover under the influence of this agent (13,15,28). Nevertheless, malabsorption of lipid is minimal in normal subjects receiving cholestyramine in a dose of 16 g/day (34).…”

Section: Study Proceduressupporting

confidence: 86%

“…The exchangeable taurocholate pool determined from the amount of administered 14C activity and the extrapolated bile acid specific activity at to (Table I) (23)(24)(25)(26). The bile acid binding capacity of cholestyramine has been adequately docunmented both by in vitro studies (27), as well as determinations in vivo of increased fecal bile acid loss and increased cholesterol turnover during its administration (13,15,28). The present observations demonstrate that cholestyramine administration decreased the enterohepatic circulation of the primary bile acid taurocholate (Table I) as well as recirculation of its major bacterial product, deoxycholate (Table III).…”

Section: Study Proceduresmentioning

confidence: 50%

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Effect of cholestyramine on bile acid metabolism in normal man

Garbutt¹,

Kenney²

1972

J. Clin. Invest.

126

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A B S T R A C T The effect of cholestyramine administration on the enterohepatic circulation of bile acids was studied in eight normal volunteers. In six subjects the metabolism of sodium taurocholate-'4C was determined after its intravenous injection before and during the 6th wk of cholestyramine administration, 16 g/day. In two subjects, the metabolism of cholic acid-14C was observed before and during the 2nd wk of cholestyramine, 16 g/day. Bile acid sequestration resulted in a more rapid disappearance of the injected primary bile acid and its metabolic products. The composition of fasting bile acids was promptly altered by cholestyramine to predominantly glycine-conjugated trihydroxy bile acid. In four subjects, unconjugated bile acid-14C was administered during cholestyramine administration; the relative proportion of glycine-conjugated bile acid-'C before enterohepatic circulation was similar to the relative proportion of unlabeled glycine-conjugated bile acid present in duodenal contents after an overnight fast, indicating that a hepatic mechanism was responsible for the elevated ratios of glycine-to taurine-conjugated bile acid (G: T ratios) observed. The relative proportions of both dihydroxy bile acids, chenodeoxycholic and deoxycholic, were significantly reduced. Steatorrhea did not occur, and the total bile acid pool size determined after an overnight fast was unaltered by cholestyramine. These findings suggest that in normal man bile acid sequestered from the enterohepatic circulation by cholestyramine is replaced by an increase in hepatic synthesis primarily via the pathway leading to production of glycocholic acid.

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Section: Study Proceduressupporting

confidence: 86%

Section: Study Proceduresmentioning

confidence: 50%

Effect of cholestyramine on bile acid metabolism in normal man

Garbutt¹,

Kenney²

1972

J. Clin. Invest.

126

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“…In the previous report (9) Since the three sets of studies reported here were all carried out for the same medium-term duration, it is likely that the studies can be compared with each other, and that they provide a quantitatively valid estimate of the effects of therapy on certain parameters, namely the production rate, the size, and the turnover rate of pool cholesterol, therefore, an increased rate of hepatic biosynthesis would be anticipated. Decreased absorption of cholesterol, reflected in an increased excretion of neutral sterol, has, however, been seen in some but not in all patients studied (6,14). Accordingly, other effects of the resin on hepatic synthesis of cholesterol are probably also involved.…”

mentioning

confidence: 92%

“…One effective agent is cholestyramine, an anion-exchange resin that binds bile acids in the intestine and prevents their reabsorption (1,6,(12)(13)(14). This drug results in a greatly increased fecal excretion of acidic steroids (6,14), and secondarily in an increased catabolism and synthesis of cholesterol and a reduced plasma cholesterol level.…”

mentioning

confidence: 99%

The Effects of Colestipol Resin and of Colestipol Plus Clofibrate on the Turnover of Plasma Cholesterol in Man

Goodman¹,

Noble²,

Dell³

1973

J. Clin. Invest.

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A B S T R A C T Studies were conducted to determine the effects of colestipol hydrochloride, a new bile acidsequestrant resin, on some of the parameters of cholesterol turnover and metabolism in man. Three normal volunteers and eight hyperlipidemic patients participated in three sets of cholesterol turnover studies carried out at intervals of approximately 1 yr. The effects of colestipol were assessed by comparing the results obtained before therapy with those obtained on repeat study after several months of resin therapy. Colestipol treatment significantly reduced the serum cholesterol concentration (mean reduction 21%), and produced a large increase in the production rate of cholesterol (mean 86%) and in the turnover rate of cholesterol in pool 1 (mean 46%). The values of the intercompartmental rate constants and of the size of the rapidly exchangeable pool were unchanged with therapy.The turnover studies were carried out for 12-13 wk, and were analyzed according to a two-pool model. Although long-term studies of cholesterol turnover conform to a three-pool, rather than a two-pool model, the present studies probably provide a valid estimate of the effects of therapy on certain parameters, namely the production rate, the size, and the turnover rate of pool 1.Repeated studies in four untreated subjects showed a striking constancy with time for the kinetic parameters for each subject. four patients, and reduced the triglyceride level in all four patients. Addition of clofibrate to the treatment program produced only small decreases in the production rate, which were not significantly different from the small decreases seen in two patients who were continued (and restudied) on colestipol alone. The findings do not support the suggestion that clofibrate can block the increased rate of cholesterol synthesis and turnover resulting from bile acid-sequestrant treatment. The effects on serum lipids, however, make the combined drug therapy potentially quite useful. INTRODUCTION Considerable information is now available about the turnover of plasma cholesterol in normal and in hyperlipidemic humans. When kinetic studies are conducted

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“…Coronary arteriograms were obtained before and after [3][4] Brachiocephalic or peripheral arteriograms were repeated in three and five patients, respectively, after 3-4 years of medical therapy. None developed new lesions or showed significant progression of the basic arterial disease.…”

Section: Methodsmentioning

confidence: 99%

Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia.

Kuo¹,

Hayase²,

Kostis³

et al. 1979

Circulation

129

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SUMMARY Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type 1I hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean ± SEM): C and LDL-C from 412.7 ± 24.4 and 331.1 ± 22.8 to 270 ± 11.0 and 188.1 ± 13.8, respectively (p < 0.001 in each instance) over 7-71/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances.COLESTIPOL, a tetraethylene-pentamine and epichlorhydrin copolymer, is a synthetic anionic bile acid-binding resin which sequestrates bile acids in the intestinal tract to reduce their reabsorption.1 2 This stimulates an increased rate of hepatic sterol synthesis. However, if increased hepatic cholesterol biosynthesis is insufficient to compensate for the exaggerated cholesterol degradation into bile acids, hepatic cholesterol pool may be reduced,3 and will result in lowering of plasma cholesterol concentration. Several colestipol studies of different durations in man have reported serum cholesterol reductions of 14-20% from the pretreatment or placebo treatment levels.2' [4][5][6][7][8] Since hypercholesterolemia in patients with familial type II hyperlipoproteinemia is caused at least partially by a decrease in cholesterol-rich low density

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Effect of cholestyramine on the fecal excretion of intravenously administered cholesterol-4-14C and its degradation products in a hypercholesterolemic patient

Cited by 71 publications

References 30 publications

Effect of cholestyramine on bile acid metabolism in normal man

Effect of cholestyramine on bile acid metabolism in normal man

The Effects of Colestipol Resin and of Colestipol Plus Clofibrate on the Turnover of Plasma Cholesterol in Man

Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia.

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