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PubMed1984

Effects of cholestyramine and colestipol on the plasma concentrations of propranolol.

The effect of equivalent hypolipidaemic doses of cholestyramine (8 g) or colestipol (10 g) on the plasma concentrations of propranolol and 4'-hydroxypropranolol was studied in 12 normal volunteers following the oral administration of 120 mg of normal release propranolol tablets. When two doses of either cholestyramine or colestipol were administered prior to the propranolol, the peak plasma concentrations and area under the curve for both propranolol and the metabolite 4'-hydroxypropranolol were reduced significantly (P less than 0.05). We conclude that the drug interaction between cholestyramine or colestipol and propranolol leads to significant reductions in plasma concentrations of propranolol and 4'-hydroxypropranolol which may cause a clinically diminished effect for a given dosage. Therefore, patients should be observed when either of these resins are added to or deleted from a therapeutic regimen.

Adult↗
PubMed1983

The effects of colestipol hydrochloride on serum lipoprotein lipid and apolipoprotein B and A-I concentrations in children heterozygous for familial hypercholesterolemia.

The effects of colestipol hydrochloride on serum lipoprotein lipid and apolipoprotein B and A-I concentrations in children heterozygous for familial hypercholesterolemia. Acta Paediatr Scand, 72:81, 1983.--Colestipol hydrochloride was administered to 28 children with familial hypercholesterolemia type II-A, and its effects on serum lipoproteins were tested against a placebo in a cross-over design. All children consumed a diet low in cholesterol and high in linoleic acid. Colestipol therapy resulted in a 15.7% decrease in serum very low plus low density lipoproteins and in a 13.5% decrease in serum apolipoprotein B. High density lipoprotein cholesterol, serum apolipoprotein A-I and serum triglycerides remained unaltered.

Adolescent↗
PubMed1996

Colestipol tablets in adolescents with familial hypercholesterolaemia.

The objective of this study was to examine palatability and side effects of the new tablet formulation of colestipol. A clinical series of 23 boys and 4 girls aged 10-16 years with heterozygous familial hypercholesterolaemia were given 2-12 g colestipol daily for 6 months in an open study. There were no serious side effects. The median reduction in low density lipoprotein cholesterol level was 20%. All preferred the tablets to resin granules they had tried previously. We conclude that low-dose colestipol tablets appear to be safe and effective, and are preferred by adolescents.

Adolescent↗
PubMed1996

Effects of colestipol alone and in combination with simvastatin on apolipoprotein B metabolism.

The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).

Adult↗
PubMed1979

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

Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type II 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 less than 0.001 in each instance) over 7--7 1/2 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.

Adult↗
PubMed1981

Use of colestipol in a patient with digoxin intoxication.

The steroid-binding drug colestipol was administered to a patient with digoxin intoxication and the serial digoxin levels were measured. The actual half-life of elimination of digoxin was 55 hours, whereas the predicted half-life calculated from standard pharmacokinetic equations was at least 85 hours. Colestipol presumably interrupts the enterohepatic recycling of digoxin and enhances its fecal excretion. This is the first documented report of the successful use of colestipol for digoxin intoxication.

Colestipol↗
PubMed2001

Colestipol-induced hepatotoxicity.

A 65-year-old man with type IIa dyslipidemia who received flavored colestipol granules 2 scoops/day for 3 months developed asymptomatic hepatotoxicity. Several of his liver enzymes were elevated 10 times the upper limit of normal. One week after discontinuing colestipol, serum transaminases fell dramatically, with some returning to normal limits. Four weeks after colestipol was discontinued, all liver function tests were normal. Rechallenge was not attempted. Other potential causes of hepatocellular injury were evaluated. Bile acid-binding resins commonly are administered to treat type IIa dyslipidemia. Despite extensive use of the resins, significant elevations of transaminase levels are rare. Because the exact mechanism of bile acid resin-induced hepatotoxicity is unknown, high-risk patients may require liver function test monitoring and education on hepatotoxic side effects.

Aged↗
PubMed1984

Probucol with colestipol in the treatment of hypercholesterolemia.

The effects of therapy with 1 g of probucol and 20 g of colestipol were compared with those of the drugs used singly on 47 patients with hypercholesterolemia in a double-blind, double-placebo, diet-controlled, crossover trial that lasted 18 months. The probucol and colestipol combination, but neither drug alone, reduced mean serum low-density-lipoprotein (LDL)-cholesterol levels from 242 +/- 51 (SE) mg/dL during the diet and placebo phase to 171 +/- 41 mg/dL. Probucol significantly lowered high-density-lipoprotein (HDL)-cholesterol levels and increased LDL:HDL-cholesterol ratios. Combination therapy did not change LDL:HDL cholesterol ratios. Probucol alone or in combination reduced very-low-density-lipoprotein cholesterol levels, despite concomitant elevations of serum triglyceride levels caused by colestipol in the combination protocol. Gastrointestinal side effects of single drugs were abolished when drugs were used in combination. Compared with the values in the diet-placebo phase, LDL-cholesterol levels were reduced by more than 20% in 81% of patients, by more than 30% in 49%, and by more than 40% in 17%. This drug combination proved to be safer and have greater hypocholesterolemic effects in more patients than other marketed drug treatments.

Adult↗
PubMed1980

Fat-soluble vitamin concentrations in hypercholesterolemic children treated with colestipol.

In summary: (1) Colestipol therapy plus diet reduced total cholesterol 19 +/- 3% in 11 hypercholesterolemic children after two months and 13 +/- 5% after two years in five children. (2) Diet therapy did not significantly reduce serum concentration of any of the fat-soluble vitamins or folate. (3) During 24 months of colestipol therapy plus diet serum vitamin A and E concentrations did decrease in the five patients with good drug adherence (vitamin A, 68 +/- 11 vs 35 +/- 4 microgram/100 ml, P less than .005) (vitamin E, 14 +/- 1 vs 11 +/- 1 microgram/ml, P less than .05). However, those concentrations remained within normal limits. (4) Colestipol therapy plus diet had no effect on prothrombin time, serum 25-hydroxycholecalciferol, folate, or calcium metabolism (as studied by sequential determination of serum total and ionized calcium phosphorus, alkaline phosphatase, and parathyroid hormone).

Adolescent↗
PubMed1977

[Colestipol by hypercholesteremia in diabetics].

The study comprises 90 diabetic patients with hypercholesterolemia. They received colestipol, a basic anion exchange resin, which binds the bile acids in the intestinal tract and thus prevents its enterohepatic circulation. The constant regeneration of bile acids from cholesterol leads to a decrease of the cholesterol level. A significant reduction of the cholesterol level was achieved in 73 of 85 evaluated cases. The observed triglyceride levels showed a different behaviour. All other laboratory data, especially the blood-sugar level, remained unchanged under the treatment with colestipol. Colestipol was well tolerated and, due to its neutral taste, was readily taken by the patients. Only a few patients suffered from slight constipation which did not lead to discontinuation of the treatment.

Colestipol↗
PubMedDate not supplied

Effect of pharmaceutical care on optimum colestipol treatment in elderly hypercholesterolemic veterans.

We conducted a prospective trial to determine whether a formal, integrated pharmaceutical care plan can enhance patient acceptance and compliance with colestipol therapy and improve outcomes. Forty patients with hypercholesterolemia were equally divided and assigned to either a usual care or pharmaceutical care group. In the pharmaceutical care group compared with the usual care group, after 52 weeks, colestipol therapy resulted in a greater reduction in total cholesterol (12.5% vs 7.3%), low-density lipoprotein cholesterol (LDL-C; 16% vs 9.4%), and LDL-C:high-density lipoprotein cholesterol (HDL-C) ratio (24.4% vs 12.2%, p < 0.05). The percentage of patients who achieved their LDL-C goal at week 52 was much greater in the pharmaceutical care group (29.4%) than in the usual care group (5.0%, p < 0.05). Co-management by a physician and a pharmacist of hypercholesterolemic veterans treated with colestipol can enhance patient acceptance of the drug, LDL-C reduction, and achievement of therapeutic goals.

Aged↗
PubMed1991

Quaternized colestipol, an improved bile salt adsorbent: in vitro studies.

Colestipol.HCl (col-HCl) was quaternized with methyl iodide to form col-CH3l. The in vitro binding capacities of the quaternized and protonated resins in water and in Tris-HCl buffer (0.0015 and 0.0025 M, pH 7.0) at approximately 22 degrees C for sodium glycocholate (NaGC) was determined by reversed-phase HPLC. The binding capacities were found to depend on the adsorption medium. In water, the binding capacity of col-CH3l was 30% greater than that of its protonated form. In Tris-HCl buffer at pH 7.0, the binding capacities of the resins were similar. When the quaternized colestipol was converted to its chloride form, the binding capacity for NaGC in Tris-HCl increased significantly and was 30% greater than that for its protonated analogue. In Cotazym 65B-water, a medium used to test the binding capacity of the resins in the presence of various agents (to try to simulate intestinal conditions), the binding capacity of the quaternized resin was again greater than that of its protonated form. Quaternization thus increases the in vitro binding capacity of colestipol for the glycocholate anion.

Adsorption↗
PubMed1992

Polymeric sorbents for bile acids. I: Comparison between cholestyramine and colestipol.

Isotherms for the sorption of bile acids at 20 degrees C, in tris(hydroxymethyl)aminomethane.HCl(tris) and KH2PO4-NaOH (phosphate) buffers (pH 7.4), indicate that the binding by cholestyramine and colestipol is mainly through ionic linkages, although hydrophobic interactions are also of importance. Cholestyramine has a higher sorption capacity for bile acids, in both buffers, than colestipol. The chloride form of cholestyramine has a higher capacity for cholate in tris buffer than the iodide form. Increased ionic strength of the medium leads to decreased amounts of sorption.

Absorption↗
PubMed1977

Effects of colestipol hydrochloride and neomycin sulfate on cholesterol turnover in the rat.

Three groups of male rats were fed diets containing the bile acid sequestrant colestipol hydrochloride (1%), neomycin sulfate (0.25%), or basic diet during the test. After 15 days, each rat was injected IV with 3.9 muCi cholesterol-1,2(-3)H complexed with serum lipoproteins; specific radioactivity of the total serum cholesterol was measured at several time intervals for a period of 7 weeks. Computer analysis of the data indicated that the turnover of cholesterol could best be fitted by a three-pool model. In pool 1, colestipol HC1 caused a significant increase in production rate (10.09 to 15.96 mg/day) and the excretion rate constant (0.53 to 0.79 day-1) of cholesterol without significantly altering the size of the pool or serum cholesterol concentrations. These results are compatible with an agent capable of binding bile acids in the rat but do not cause a decrease of the sterol pool because of an adequate compensatory increase in cholesterol biosynthesis. Neomycin SO4 caused a significant reduction in serum cholesterol (9%) without altering turnover parameters and apparently exerts its hypocholesterolemia by some mechanism other than bile acid sequestration.

Animals↗
PubMed1998

Role of colestipol in the treatment of hyperthyroidism.

The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves' disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) > or =5 nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT-3<5 nmol/l). Crook's clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (WO), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean+/-SE) at W1 by 40.8+/-2.6% of WO in Group1 and by 29.2+/-2.4% in Group 2 (p<0.001), and down further to 47.8+/-3.0% at W2 in Group 1, and 40.6+/-2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean+/-SE) from WO to W1 by 31.7+/-2.7% in Group 1 and by 16.2+/-3.1% in Group 2 (p=0.005), and down to 49.1+/-2.8% of WO at W2 in Group 1 and to 38.7+/-3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.

Adult↗
PubMed1986

Effects of combined probucol-colestipol treatment for familial hypercholesterolemia and coronary artery disease.

To evaluate the effect of hypercholesterolemic treatment on coronary artery disease in patients known to be susceptible to disease progression, 44 patients with familial hypercholesterolemia and coronary artery disease were started on a lipid-lowering diet and either probucol (1 g/day) or colestipol (30 g/day). After 5 months of monotherapy, all patients went on a regimen of diet and 2-drug therapy. To date, combination therapy has continued for 3.4 to 4.1 years, and has resulted in the following changes from baseline in mean serum lipid levels: -48.5% in total cholesterol, -53.3% in low density lipoprotein cholesterol, -30.0% in high density lipoprotein cholesterol and +14.5% in triglycerides. The reduction in low density lipoprotein cholesterol apparently improved the clinical status of these patients despite the associated drop in high density lipoprotein cholesterol. In the 19 patients who underwent coronary arteriography before admission to the study, follow-up arteriograms showed that combined treatment stabilized the progression of established lesions and prevented the formation of new ones. Side effects occurred mainly with monotherapy and during the early phase of combination therapy. Reactions included diarrhea, constipation, other vague abdominal symptoms, headache and joint stiffness. In all instances, the side effects gradually subsided after the institution of combination therapy. The combination of probucol and colestipol plus diet appears to be effective in treating most patients with familial hypercholesterolemia.

Adult↗
PubMed1978

Preparation of [14C]colestipol hydrochloride and its disposition in the human, dog and rat.

Colestipol hydrochloride, a polymeric, ion-exchange type, hypocholesterolemic agent, acting by sequestering bile acids, was labeled with carbon-14. The disposition of the labeled material was studied in the human, dog and rat. The extent of absorption from the gastrointestinal tract, as judged by urinary excretion of radioactivity, was very small and correlated well with the contents of water-soluble and dialyzable materials in the colestipol hydrochloride. Results were consistent with the dialyzable material in the drug being the absorbable species.

Animals↗
PubMed1982

"Low dose" colestipol in children, adolescents and young adults with familial hypercholesterolemia.

The effect of colestipol on plasma lipids and lipoproteins was studied in children, adolescents and young adults with familial hypercholesterolemia. O.125 g or 0.25 g/kg body weight were given in randomized sequence for period of 4 weeks. Total cholesterol was lowered by 13 and 18% with the smaller and larger dose , respectively, and LDL cholesterol lowered by 15% with the smaller and 12% with the larger dose. HDL cholesterol rose by 18 an 32%. LDL composition before and during the study was abnormal due to a markedly reduced triglyceride content. "Low-dose" colestipol is less effective lowering total plasma and LDL cholesterol than conventional doses but may, due to very few side effects, by advantageously used in cases of familial hypercholesterolemia when plasma cholesterol levels after dietary management are only 15-20% above normal.

Adolescent↗