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PubMed1995

The effects of colestipol tablets compared with colestipol granules on plasma cholesterol and other lipids in moderately hypercholesterolemic patients.

The purpose of this study was to investigate and compare the efficacy, safety, and patient acceptability of a new formulation of colestipol, colestipol tablets (T), with those of colestipol granules (G), in a randomized, double-blind, placebo-controlled, multicenter study. Three hundred and seventeen patients with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet (NCEP Step I diet), and had low-density lipoprotein cholesterol (LDL-C) levels > or = 4.14 mmol/l (160 mg/dl) and < or = 6.46 mmol/l (250 mg/dl) were studied. Study medication was taken twice a day, with breakfast and supper, for 8 weeks. The six parallel treatment groups consisted of colestipol tablets 2 g b.i.d. and 8 g b.i.d., matching placebo tablets b.i.d., colestipol granules 2 g b.i.d. and 8 g b.i.d., and matching placebo granules b.i.d.. Study endpoints included absolute change and percentage change from baseline in selected lipid, lipoprotein, and apolipoprotein measurements; LDL-C lowering was the primary efficacy endpoint. Treatment with colestipol tablets and colestipol granules resulted in virtually identical, statistically significant (P < or = 0.05) reductions of LDL-C, total cholesterol (TC), TC/HDL-C, and apolipoprotein B (apo B). Compared with placebo, all active treatments (tablets 4 g/day, tablets 16 g/day, granules 4 g/day, granules 16 g/day) significantly reduced LDL-C (12%, 24%, 12%, 25%, respectively), TC (7%, 15%, 8%, 15%, respectively), TC/HDL-C (8%, 14%, 9%, 15%, respectively) and apo B (12%, 20%, 13%, 22%, respectively). All active treatments significantly increased lipoprotein particle AI (LpAI) (5%, 23%, 14%, 18%, respectively). VLDL-C and triglycerides increased significantly in the high-dose groups. The proportions of patients reporting adverse events, largely gastrointestinal-related, were not different among the active treatment groups. The treatments were well-tolerated, and no drug-related serious adverse events were reported. Patients experienced with granule medication prior to this study preferred tablets over granules. This study demonstrates that colestipol tablets are an effective treatment to reduce LDL-C in patients with primary hypercholesterolemia, are equivalent to colestipol granules, are well-tolerated, and are preferred over granules by patients.

Adult↗

PubMed1973

The effects of colestipol resin and of colestipol plus clofibrate on the turnover of plasma cholesterol in man.

Studies were conducted to determine the effects of colestipol hydrochloride, a new bile acid-sequestrant 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. The production rate was particularly constant from year to year for a given subject, and showed a pooled standard deviation of only 3%. The findings suggest that the total body turnover of cholesterol is under close homeostatic control in an integrated manner. Combined drug therapy with colestipol plus clofibrate further reduced the serum cholesterol level in three of 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.

Adult↗

PubMed1981

Plasma lipid concentrations and lecithin:cholesterol acyltransferase activity in normolipidemic subjects given fenofibrate and colestipol.

Plasma lipids and lipoprotein cholesterol concentrations and lecithin:cholesterol acyltransferase activity were measured in 7 normolipidemic subjects before, and 7 days after, the administration of fenofibrate (300 mg daily) and colestipol (15 g daily) taken separately or simultaneously. Fenofibrate provoked a significant decrease in the mean plasma triglycerides (26%) and cholesterol (10%) concentration; only plasma cholesterol concentrations were significantly lowered by colestipol (26%). The cholesterol lowering effects of the two drugs were additive as was observed when colestipol was added to fenofibrate. The mean plasma high density lipoprotein cholesterol (HDL-C) concentration was significantly increased by fenofibrate (10%) and when colestipol was added to fenofibrate (15%), but not by colestipol alone. Both fenofibrate and colestipol caused significant reduction of the mean plasma low density lipoprotein cholesterol (LDL-C) concentration and the mean plasma LDL-C/HDL-C ratio (13% and 18%, respectively, with fenofibrate, 44% and 52% with colestipol, and 53% and 62% with colestipol added to fenofibrate). The mean plasma fractional esterification rate was significantly increased by 25% and 12%, respectively, with fenofibrate and colestipol when taken separately, and still more (91%) when colestipol was added to fenofibrate. The mean plasma molar esterification rate was significantly lowered by colestipol, but remained unchanged with the other drug regimens. This study shows that fenofibrate and colestipol given to normolipidemic subjects can induce in a very short period of time (7 days) marked changes in lipoprotein metabolism. Interpretations of the findings in relation to lipoprotein metabolism are discussed.

Adult↗

PubMed2002

Effect of concomitant colestipol hydrochloride administration on the bioavailability of diltiazem from immediate- and sustained-release formulations.

Effects of concomitant colestipol administration on plasma concentrations of diltiazem and desacetyldiltiazem from immediate-release (IR) and sustained-release (SR) formulations were assessed in two studies. In the first study, 12 subjects received 120-mg diltiazem hydrochloride (diltiazem) SR capsules or 120-mg diltiazem IR tablets administered alone and in combination with colestipol hydrochloride (colestipol). Following concomitant administration of SR diltiazem with colestipol, AUC(0-infinity ) and C(max), respectively, were 22 and 36% less, and were 27 and 33% lower for IR diltiazem. In the second study, subjects received 120-mg diltiazem SR capsules at staggered times, without colestipol, 1 h prior to or 4 h following multiple doses of colestipol. A 17% decrease in AUC(0-infinity ) was observed when diltiazem was taken 1 h before colestipol was given, and a 22% decrease when diltiazem was taken 4 h after colestipol, relative to diltiazem SR alone. C(max) values were similarly decreased. Results from these two studies show that colestipol can cause a significant decrease in diltiazem absorption from both IR and SR dosage forms. Staggering the administration of colestipol and diltiazem SR did not blunt this effect, indicating that concomitant administration of diltiazem and colestipol should be used with caution, and that the efficacy of diltiazem should be monitored to assure adequate dosing.

Adolescent↗

PubMed1990

Apparent reduced absorption of gemfibrozil when given with colestipol.

Colestipol and gemfibrozil may be used in combination to lower serum cholesterol and triglycerides. Since colestipol is known to bind certain anionic drugs, we studied the effect of colestipol on the pharmacokinetics of gemfibrozil in 10 patients with elevated serum cholesterol and triglycerides. Each patient received 600 mg of gemfibrozil by mouth during four different studies. Gemfibrozil was given randomly either alone, with, 2 hours before, or 2 hours after 5 grams of colestipol. The serum gemfibrozil concentration time curves were similar when gemfibrozil was given alone or two hours before or after colestipol. There was also no statistical difference in peak gemfibrozil concentration (Cmax), time to Cmax (tmax), area under the curve (AUC), or serum elimination half-life (t1/2) between any of these three treatments. However, when colestipol was given with gemfibrozil, there was a decrease in AUC (43.6 +/- 21.9 mg*hr/L) compared with gemfibrozil given alone (62.6 +/- 10.3 mg*hr/L) which was statistically different by both ANOVA and paired t-test. This finding suggests a decrease in gemfibrozil bioavailability. Cmax when colestipol was given with gemfibrozil (14.7 +/- 6.6 mg/L) was not statistically different from gemfibrozil alone (20.1 +/- 4.9 mg/L). However, the mean serum concentrations when gemfibrozil was given with colestipol were significantly lower at the 0.5, 1.0 and 1.5 hour sampling times when compared to the other regimens. Gemfibrozil serum elimination half-life was not significantly altered by combination with colestipol. The data suggest a reduction of gemfibrozil bioavailability when colestipol is administered concomitantly. Separating the administration of these two drugs by at least two hours will avoid this drug interaction.

Aged↗

PubMed1983

Modification of the carcinogenic process in colorectal cancer by endogenous and exogenous factors: effect of colestipol hydrochloride on tumors induced by dimethylhydrazine.

The effect of the bile acid sequestrant, colestipol hydrochloride, on the incidence of dimethylhydrazine-induced tumors of the large intestine was determined in male Swiss mice. The subcutaneous administration of dimethylhydrazine (15 mg/kg) produced tumors in approximately 89% of the animals with an average of 1.70 tumors per tumor-bearing animal. When carcinogen-treated animals received dietary colestipol (0.52%, w/w) from 4 weeks prior to the first injection of dimethylhydrazine until the time of death, there was an increase in the number of tumors per tumor-bearing animal to 2.23. In an attempt to understand the nature of this enhancement, animals were administered dietary colestipol at different times in relation to the administration of the carcinogen. The number of tumors per tumor-bearing animal for the different protocols was: post-initiation colestipol exposure, 1.70; colestipol exposure concomitant with dimethylhydrazine, 1.41; pre-initiation colestipol exposure, 2.23. Thus, colestipol appeared to function both as an anticarcinogen and as a promoter (pre-initiation). Since colestipol has the capacity to bind a number of chemical agents, the different biological effects probably reflect the multifactorial nature of colorectal cancer with the end result dependent on the balance between opposing factors. The selective administration of colestipol in relation to carcinogen administration may prove useful in elucidating the various factors involved in the etiology of this disease.

Animals↗

PubMed1995

Combination therapy with colestipol and psyllium mucilloid in patients with hyperlipidemia.

OBJECTIVE: To test whether combining psyllium mucilloid with half the usual dose of colestipol reduces the adverse effects associated with colestipol and maintains or increases its efficacy in the treatment of hyperlipidemia. This strategy might make bile acid sequestrants, which are seldom used because they cause adverse effects such as bloating and constipation, more tolerable and less expensive. DESIGN: A randomized, parallel-group, double-blind, controlled trial. SETTING: An outpatient clinic in a tertiary care hospital. PATIENTS: 121 patients who had moderate primary hypercholesterolemia (total cholesterol level > 6 mmol/L and < 8 mmol/L; triglyceride level < 3 mmol/L) after following a low-fat diet for 1 year (National Cholesterol Education Program Step Two diet). INTERVENTION: 5 g of cellulose placebo; 5 g of colestipol; 2.5 g of colestipol plus 2.5 g of psyllium; or 5 g of psyllium three times daily before meals for 10 weeks. MAIN OUTCOME MEASURES: At baseline and at weeks 4 and 10, fasting blood lipid levels and apoprotein concentrations were measured and a quality-of-life instrument was completed. RESULTS: A combination of 2.5 g of psyllium and 2.5 g of colestipol was better tolerated than and as effective as either 5 g of colestipol alone or 5 g of psyllium alone. The combination therapy and colestipol alone did not differ significantly with respect to changes in individual lipid values. The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL) was reduced by 18.2% (95% CI, 12.3% to 24%) with the combination therapy; by 10.6% (CI, 2.0% to 15.4%) with colestipol alone; by 6.1% (CI, 1.5% to 10.6%) with psyllium alone; and by 0.1% (CI, -4.8% to 7%) with placebo (P = 0.0002). Combination therapy reduced the ratio of total cholesterol to HDL significantly more than did colestipol alone or psyllium alone (P < 0.05). CONCLUSIONS: These findings suggest that adding psyllium to half the usual dose of bile acid sequestrant resins maintains the efficacy and improves the tolerability of these resins.

Adult↗

PubMed1976

Effects of colestipol hydrochloride on drug absorption in the rat II.

The effects of colestipol hydrochloride, a hypocholesterolemic bile acid-binding anion-exchange polymer, on the GI absorption of drugs commonly used in humans were studied in the rat. Colestipol hydrochloride was given by gavage in single doses of 71.5 or 214.5 mg/kg, equivalent to 5 or 15 g, respectively, in a 70-kg human; controls received equivalent amounts of microcrystalline cellulose. Single oral doses of labeled drugs were given concurrently with colestipol hydrochloride or microcrystalline cellulose at the human therapeutic dose range on a milligrams per kilogram basis. Subsequent changes in serum drug levels were measured at several time periods, and absorption was evaluated as the total area under the time-concentration curve. Colestipol hydrochloride at either dose did not significantly alter the absorption of 6-14C-nicotinic acid, 7-3H-tetracycline, 35S-chlorpromazine, 12alpha-3H-digoxin, warfarin (alpha-14C-benzyl), or clofibrate (14C-carboxyl). In addition, the effects of 214.5 mg/kg of colestipol hydrochloride were compared with the same dose of cholestyramine with respect to the absorption of 3-14C-hydrochlorothiazide, 2-14C-phenobarbital, and 3H-digitoxin. Cholestyramine reduced absorption of hydrochlorothiazide by 42%, but colestipol hydrochloride had no significant effect. Neither resin altered phenobarbital or digitoxin absorption when compared with the the control, but a significant difference occurred between the two resins with digitoxin; areas under the time-concentration curve [in (dpm/0.1 ml serum) x hr] were: colestipol hydrochloride, 2001; cholestyramine, 16,300; and cellulose, 17, 067. These results indicate that colestipol hydrochloride and cholestyramine can differ in their effects on the absorption of certain drugs from the GI tract of the rat.

Animals↗

PubMed1980

Effect of colestipol on sterol metabolism in the rat.

Sterol metabolism studies using isotopic and chromatographic techniques were performed on rats fed diets supplemented with colestipol (Upjohn). Compared to controls, colestipol altered sterol metabolism dramatically. Bile acid output increased from 7.0 mg/day to 12.2 mg/day (0.42% colestipol) and 39.6 mg/day (1.67% colestipol). Daily fecal neutral sterol output and daily endogenous neutral sterol output increased 36% and 55%, respectively, on the 1.67% colestipol diet. Cholesterol absorption was reduced by colestipol feeding. Cholesterol balance increased dramatically with 1.67% colestipol administration (43.5 mg/day vs -1.0 mg/day in controls). Colestipol exerts its effect by binding bile acids and by bile acid depletion interfering with cholesterol absorption.

Animals↗

PubMed1981

Comparison of the effects of colestipol hydrochloride and clofibrate on plasma lipids and lipoproteins in the treatment of hypercholesterolemia.

The effects of colestipol HCl resin and clofibrate on plasma lipid and lipoprotein levels were compared in 65 patients with primary hypercholesterolemia. Patients were randomly assigned to treatment with colestipol (in progressive doses of 15, 20, and 30 g/day), clofibrate (2 g/day), or placebo resin; lipoprotein levels were determined at months 0, 2, 4, 6, and 9. The colestipol group received both colestipol and clofibrate during months 7 through 9 of the study. After 6 months of treatment, mean plasma total cholesterol fell from 333 to 266 (P less than 0.01) on colestipol, and from 329 to 270 (P less than 0.05) on clofibrate. More patients responded, however, to colestipol than to clofibrate. Both drugs also produced significant reductions in LDL cholesterol levels, and clofibrate lowered plasma triglycerides as well. HDL cholesterol level did not change significantly on either medication. The placebo group showed no change in any of the parameters studied. A significant difference was not observed between the effects of 15 g/day of colestipol and those of the higher doses studies. Addition of clofibrate to colestipol did not enhance the latter's hypocholesterolemic action.

Cholesterol↗

PubMed1976

The effect of colestipol on digitoxin plasma levels.

The effect of colestipol (colestipol hydrochloride; U-26 597 A), a copolymer of tetraethylenepentamine and epichlorhydrine, on plasma digitoxin levels has been investigated. Recently, it has been stated that colestipol decreases the enterohepatic circulation and the plasma half-life of digitoxin. Colestipol was administered to 11 patients having a digitoxin plasma level which is generally accepted to be above the therapeutic range (greater than 40 ng/ml). The elimination rate of digitoxin measured by serial radioimmunoassay in these colestipol treated patients was compared with the elimination rate of digitoxin in 11 patients not treated with colestipol. The results of this study did not demonstrate a significant difference in the mean (+/- S.D.) digitoxin plasma half-life between the colestipol treated (6.3 +/- 1.3 days) and the non-colestipol treated patients (6.8 +/- 1.0 days).

Antidotes↗

PubMed1984

Low-dose colestipol plus probucol for hypercholesterolemia.

The hypocholesterolemic and adverse effects of colestipol, 20 g/day, and colestipol, 10 g/day combined with probucol, 1 g/day, were compared. A double-placebo, diet-controlled, crossover trial that lasted 19 months was undertaken on 22 hypercholesterolemic patients who had low-density lipoprotein (LDL) cholesterol levels greater than 180 mg/dl after 3 months of diet and placebo treatment. Uniformity of diet and physical activity were monitored throughout the study. Compared with baseline values after 3 months on diet-placebo treatment, "combined" therapy reduced LDL cholesterol by more than 20% in 15 patients, more than 25% in 9 patients and more than 45% in 2 patients. Treatment with "half-dose" colestipol and probucol resulted in the greatest mean LDL cholesterol reduction, from 239 mg/dl during diet-placebo period to 170 mg/dl; the difference was not statistically significantly different from the reduction to 180 mg/dl with 20 g of colestipol alone. Fifteen patients showed the greatest reduction in LDL cholesterol after combined therapy. Probucol produced statistically significant reductions in very low density lipoprotein and high-density lipoprotein cholesterol. The major gastrointestinal side effects of single therapy with colestipol (constipation) and probucol (diarrhea) were ameliorated or abolished by concomitant administration. Probucol-colestipol co-administration allowed a 50% reduction in the colestipol dosage, with similar efficacy and improved tolerability and reduced mean serum LDL cholesterol with a frequency and magnitude rarely seen with other hypocholesterolemic treatments. Hypercholesterolemic persons who cannot tolerate full doses of resins may receive equal benefit by half the dose if probucol is added to the regimen.

Adult↗

PubMed1984

Colestipol and energy restriction as an approach to hasten removal of PBBs from chickens.

Male White Leghorn chickens were fed either 0.1 or 1.0 ppm fireMaster FF-1 (FF-1) for 21 d. During the withdrawal phase, the chickens were fed 0, 0.5, or 2.5% colestipol hydrochloride, and anion exchange resin. Also, calories were restricted to 80% of control intake within certain groups during the first 14 d in each of 2 consecutive 21-d withdrawal periods. In the caloric-restricted groups, colestipol was fed at 0, 0.625, or 3.125% to yield equal daily intake of colestipol to those fed 0, 0.5, or 2.5% concentrations. During the first 21 d of withdrawal, colestipol at 2.5-3.125%, but not 0.5-0.625%, hastened excretion of polybrominated biphenyls (PBBs) by 50%. During d 22-42 of withdrawal, a background level of PBBs contamination was detected, which tended to confound the results. Despite this, higher levels of colestipol lowered overall body burdens of PBBs by 80% in comparison to the overall level of residues in the other groups of chickens, and by 20% in comparison to their own levels 21 d earlier. Dietary colestipol resulted in chickens with lower carcass lipid content. The combination of energy restriction plus colestipol at 2.5-3.125%, which had the greatest impact in reducing body weight gain and carcass lipid, seemed to be the most favorable treatments for hastening excretion of PBB residues.

Animals↗

PubMed1987

Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia.

OBJECTIVE: To compare the effectiveness of the ternary-drug combination of colestipol, niacin, and lovastatin with binary combinations of those drugs in treating patients with familial hypercholesterolemia. DESIGN: An open sequential study of serum lipoprotein responses in patients receiving diet alone (mean duration, 4 months); colestipol and niacin with diet (mean duration, 9 months); and colestipol, niacin, and lovastatin with diet (mean duration, 15 months). SETTING: Metabolic ward and lipid clinic of a university medical center. PATIENTS: Twenty-two patients with clinical characteristics of familial hypercholesterolemia (low-density-lipoprotein cholesterol, greater than 8.48 mmol/L; 21 of 22 with tendon xanthomas). INTERVENTIONS: Diet: less than 200 mg/d of cholesterol and less than 8% of total calories from saturated fat; colestipol, 30 g/d; lovastatin, 40 to 60 mg/d; and niacin, 1.5 to 7.5 g/d. MEASUREMENTS AND MAIN RESULTS: Mean total serum cholesterol and low-density-lipoprotein cholesterol levels of 4.86 +/- 0.62 mmol/L (188 +/- 24 mg/dL SD) and 2.89 +/- 0.54 mmol/L (112 +/- 21 mg/dL SD), respectively, were significantly lower during ternary-drug treatment than during colestipol-niacin treatment (p less than 0.003) or during treatment in which other possible binary combinations were given. The cholesterol content of very low-density-lipoproteins was lower and high-density-lipoprotein cholesterol levels higher during this phase than during the colestipol-niacin phase. CONCLUSIONS: Colestipol, lovastatin, and niacin are mutually complementary in treating hypercholesterolemia. This regimen produces reductions in serum cholesterol levels similar to those associated with regression of atheromatous plaques in animal studies.

Adult↗

PubMed2000

Sorption of fluoroacetate (compound 1080) by Colestipol, activated charcoal and anion-exchange in resins in vitro and gastrointestinal decontamination in rats.

The sorption of sodium fluoroacetate (FA) by activated charcoal (AC) and 5 anion exchange resins (AERs) was tested in 2 simulated gastrointestinal (GI) fluids. Each sorbent was incubated with FA in a shaker-water-bath at 37 C for 24 h. Supernatant was removed and filtered, and the concentration of FA was determined by gas chromatographic detection of the dichloroaniline derivative. Under simulated gastric conditions (0.1 M HCl at approximately pH 1.5), the sorbents removed the following proportions of FA from solution: Carbosorb AC, 87 +/- 2%; cholestyramine, 28 +/- 7%; colestipol, 96 +/- 0%; Amberlite IRA-96, 70 +/- 2%; DEAE-Sephadex, 7 +/- 4%; Chitosan, 66 +/- 2%. Under simulated intestinal conditions (0.05 M sodium phosphate at approximately pH 7.4), binding was as follows: Carbosorb AC, 68 +/- 4%; cholestyramine, 53 +/- 5%; colestipol, 46 +/- 2%; AmberliteIRA-96, 10 +/- 20%; DEAE-Sephadex, 64 +/- 7%; Chitosan, 5 +/- 2%. All findings differed significantly from control, with the exception of Amberlite IRA-96 and Chitosan in phosphate buffer, and DEAE-Sephadex in HCI. In a second study, rats were given 5 mg FA/kg, and then gavaged with 2 g/kg Carbosorb AC, colestipol or bentonite. Over 4 h, the area under the curve of serum FA versus time (AUC) decreased by 39% in the rats treated with colestipol and 42% in those treated with bentonite. In contrast, Carbosorb AC did not affect the AUC,yet increased Tmax In another study, mortality was assessed 96 h after rats were orally dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb AC, colestipol or water immediatey or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingiy, the 30-min delay resulted in lower mortality in colestipol-treated rats, (approximately 38%) compared to 100% in the group treated with Carbosorb AC. Before any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive care setting. The potential for synergistic effects with 2 or more sorbents also warrant investigating.

Adsorption↗

PubMed1975

Colestipol, clofibrate, cholestyramine and combination therapy in the treatment of familial hyperbetalipoproteinaemia.

Fifty-seven patients, mean age 26 years, suffering from familial hyperbetalipoproteinaemia (Fredrickson type lla and llb), were treated on a low cholesterol, modified polyunsaturated fat diet for a period of 6-12 weeks prior to the introduction of drug therapy. No significant reduction in the serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol or triglyceride was found. Fifty patients were then treated with colestipol for 6 weeks; total and LDL cholesterol decreased by 23%, but triglyceride levels were unaffected. During the following 6 weeks, placebo was administered, and total and LDL cholesterol returned to pretreatment levels. The patients were then randomly allocated into two groups of 16. The first group continued with clofibrate therapy, while the second group received cholestyramine. In the clofibrate group a reduction in total and LDL cholesterol of the order of 17% was noted, similar to cholestethat achieved in this group on colestipol. Triglyceride levels were 15% lower on clofibrate therapy than on colestipol. In the cholestyramine group, there was a 25% decrease in total and LDL cholesterol, compared with pretreatment levels. This reduction was similar to that found when colestipol was administered. Triglyceride values were significantly raised during cholestyramine therapy. Thirteen patients were then subjected to a 6-week period of combination therapy, either clofibrate or colestipol, or clofibrate and cholestyramine. Total and LDL cholesterol were reduced by 32% on combination therapy compared with 18% on colestipol and 23% on either clofibrate or cholestyramine alone. Furthermore, on combined therapy, triglyceride concentrations fell by 20% when compared with the levels found when colestipol, clofibrate or cholestyramine were administered on their own.

Adolescent↗

PubMed1977

Colestipol, clofibrate, and phytosterols in combined therapy of hyperlipidemia.

Studies were carried out to determine effects of combined chemotherapy in patients with hyperlipidemia. In one study, 14 patients were treated first with colestipol and then with the combination of colestipol and clofibrate. In a second study, six patients were given clofibrate followed by addition of phytosterols. The following measurements were made in most patients: (1) plasma lipid concentrations, (2) fecal excretions of neutral steroids and bile acids, and (3) lipid composition of gallbladder bile. In six patients of the first study, hepatic secretion rates of biliary lipids and pool sizes of bile acids were also estimated. In the first study, colestipol alone caused a marked increase in fecal bile acids that resulted in a sizable decrease in plasma cholesterol concentrations (average 21 percent). In several patients, however, triglycerides were increased somewhat by colestipol. Despite interruption of the enterohepatic circulation of bile acids, the bile acid pool was not reduced, since a compensatory increase took place in bile acid synthesis. Also, except in one patient who developed gallstones following institution of colestipol, saturation of gallbladder bile with cholesterol was not markedly increased by this drug alone. Addition of clofibrate frequently produced a further decrement in plasma cholesterol, and the mild hypertriglyceridemia induced by colestipol was reversed. However, colestipol plus clofibrate usually caused a striking increase in saturation of gallbladder bile. Previous studies have shown that clofibrate causes a flux of cholesterol from tissue pools by simultaneously decreasing cholesterol synthesis and increasing its excretion. To further increase cholesterol excretion, phytosterols, which block cholesterol absorption, were added to clofibrate in the second study. Although phytosterols did not cause a further reduction in plasma cholesterol in these particular patients, they nevertheless greatly enhanced cholesterol excretion.

Adult↗

PubMed1986

Controlled studies of the efficacy and safety of combined probucol-colestipol therapy.

A comprehensive clinical evaluation of the effects of combined probucol-colestipol therapy was undertaken in 71 hypercholesterolemic patients. In the first 18-month double-blind, double-placebo, crossover study, the effects of 1 g/day of probucol and 20 g/day of colestipol were compared with the drugs used singly in 47 patients. The combination decreased low density lipoprotein (LDL) cholesterol from a diet-placebo baseline of 242 +/- 51 mg/dl to 171 +/- 41 mg/dl. LDL cholesterol levels were decreased by more than 30% in 49% of patients, and by more than 40% in 17% of patients. Combined drug use eliminated the gastrointestinal side effects of single-drug administration or diminished their severity. Twenty-two patients who complained of resin-induced constipation entered a 19-month continuation trial that called for a half-dose of colestipol during combination treatment. This therapy decreased the LDL baseline level of 239 +/- 46 mg/dl by more than 25% in 41% of patients, and by more than 45% in 9% of patients. All patients were able to tolerate the modified probucol-colestipol therapy. Finally, a comparison was made between the hypocholesterolemic effects of combined probucol-colestipol therapy obtained after 1 and 3 years in 24 patients. These were sustained in all but 5 patients. Combined probucol-colestipol therapy increases the hypocholesterolemic effects and decreases the gastrointestinal side effects of either drug used alone. In patients who cannot tolerate full doses of resin, a half-dose may render the drug more acceptable without diminishing its lipid-lowering effect.

Cholesterol, HDL↗