Feasibility study of colestipol as an oral phosphate binder in hemodialysis patients.

BACKGROUND: Currently available calcium- and aluminium-based phosphate binders are dose limited because of potential toxicity, and newer proprietary phosphate binders are expensive. We examined phosphate-binding effects of the bile acid sequestrant colestipol, a non-proprietary drug that is in the same class as sevelamer. METHODS: The trial was an 8 week prospective feasibility study in stable hemodialysis patients using colestipol as the only phosphate binder, preceded and followed by a washout phase of all other phosphate binders. The primary study endpoint was weekly measurements of serum phosphate. Secondary endpoints were serum calcium, lipids and coagulation status. Analyses used random effects mixed models. RESULTS: Thirty patients were screened for participation of which 26 met criteria for treatment. At a mean dose of 8.8 g/24 h of colestipol by study end, serum phosphate dropped from 2.24 to 1.96 mmol/L (P < 0.001). Three patients required calcium supplementation. LDL cholesterol dropped from 1.75 to 1.2 mmol/L (P < 0.001). Three patients dropped out because of side effects or intolerance of the required dose. CONCLUSION: The results support the feasibility of a larger trial to determine the efficacy of colestipol as a phosphate binder and that other non-proprietary anion-exchange resins may also warrant investigation.

Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.

BACKGROUND: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies. METHODS: A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days. RESULTS AND CONCLUSIONS: The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.

In situ determination of the functional size of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase by radiation inactivation analysis.

Radiation inactivation analysis of liver pieces yielded a target size of 210 kDa for hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase [S)-mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34) from rats fed a normal diet. Feeding a diet containing mevinolin and colestipol, which causes a marked increase in enzyme activity, resulted in a reduction of the target size to 120 kDa. These results are consistent with those obtained by radiation inactivation and immunoblotting analysis of isolated microsomes and suggest that the increase in HMG-CoA reductase activity caused by these dietary agents is accompanied by a change from a dimer to a monomer form of the enzyme.

Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density.

BACKGROUND: Small, dense LDL particles are associated with coronary artery disease (CAD) and predict angiographic changes in response to lipid-lowering therapy. Intensive lipid-lowering therapy in the Familial Atherosclerosis Treatment Study (FATS) resulted in significant improvement in CAD. This study examines the relationship among LDL density, hepatic lipase (HL), and CAD progression, identifying a new biological mechanism for the favorable effects of lipid-altering therapy. METHODS AND RESULTS: Eighty-eight of the subjects in FATS with documented coronary disease, apolipoprotein B levels >/=125 mg/dL, and family history of CAD were selected for this study. They were randomly assigned to receive lovastatin (40 mg/d) and colestipol (30 g/d), niacin (4 g/d) and colestipol, or conventional therapy with placebo alone or with colestipol in those with elevated LDL cholesterol levels. Plasma hepatic lipase (HL), lipoprotein lipase, and LDL density were measured when subjects were and were not receiving lipid-lowering therapy. LDL buoyancy increased with lovastatin-colestipol therapy (7.7%; P<0.01) and niacin-colestipol therapy (10.3%; P<0.01), whereas HL decreased in both groups (-14% [P<0.01] and -17% [P<0.01] with lovastatin-colestipol and niacin-colestipol, respectively). Changes in LDL buoyancy and HL activity were associated with changes in disease severity (P<0.001). In a multivariate analysis, an increase in LDL buoyancy was most strongly associated with CAD regression, accounting for 37% of the variance of change in coronary stenosis (P<0.01), followed by reduction in apolipoprotein Bl (5% of variance; P<0.05). CONCLUSIONS: These studies support the hypothesis that therapy-associated changes in HL alter LDL density, which favorably influences CAD progression. This is a new and potentially clinically relevant mechanism linking lipid-altering therapy to CAD improvement.

"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.

Long-term trial with colestipol plus clofibrate in familial hypercholesterolemia.

Twenty subjects with familial hypercholesterolemia (12 Type IIa and 8 Type IIb), previously treated with Colestipol for 16 months, were subjected to therapy with Colestipol (15 g/day) + clofibrate (2 g/day) for 15 months. During the second treatment period these patients continued to follow the isocaloric hypocholesterolemic diet initiated during the original trial. In Type IIa patients, the association of these drugs enhanced the decrease in plasma cholesterol levels. The total mean decrease was -40 +/- 17 mg/dl (P less than 0.05). In Type IIb patients, on the other hand, the association of clofibrate with Colestipol induced an increase in plasma cholesterol levels. The total mean increase was +24 +/- 7 mg/dl (P less than 0.05). A markedly significant decrease in plasma triglyceride levels was observed in this group (- 107 +/- 30; P less than 0.01). These results seem to indicate that, in Type IIa, clofibrate increased the resin's hypocholesterolemic effect. In Type IIb, on the other hand, the association of these drugs did not seem to be indicated since a marked hypotriglyceridemic effect was accompanied by an increase in plasma cholesterol levels. These results are briefly discussed in the light of recent data obtained on the effects of Colestipol and clofibrate on lipoprotein metabolism.

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.

Long-term effects of colestipol (U-26,597 A) on plasma lipids in familial type II hyperbetalipoproteinaemia.

Results related to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolaemia, 12 with Type IIA, 8 with Type IIB and 3 homozygotes are reported. Patients were given 15 g/day active drug for a period of 12 months and a double dose (30 g/day) for a successive period of 4 months along with a low cholesterol, low saturated fat, polyunsaturated fat-rich diet. Mean cholesterol decrease was --42 +/- 18 mg/dl (P less than 0.05) after 12 months of 15 g/day Colestipol and --69 +/- 17 mg/dl (P less than 0.01) after the following 4 months of 30 g/day Colestipol. The difference between the two periods of treatment (15 g and 30 g/day was not statistically significant. A slight but not significant increase in triglyceride levels was observed. Serum uric acid showed a significant increase throughout the entire period of treatment. No malabsorption syndrome or signs of toxicity were seen. Most frequent side effects were constipation, nausea, and metheorism which, with the exception of 4 cases which were withdrawn from the study, were reported as being transitory and mild.

Results of colestipol therapy in Type II hyperlipoproteinemia.

Twenty-five patinets with well defined Type ii hyperlipoproteinemia were treated with a divided 15 g daily dose of colestipol, a bile acid sequestrant, for periods of up to 20 months. The patients were divided into 3 groups: Those with no obvious sequelae, those with arcus corneae, xanthomas, and/or xanthelasmas only, and those with atherosclerotic complications. Colestipol lowered plasma cholesterol in all 3 groups, but reduced it to normal or near-normal levels in only 9 of the 25 patients (36%). The response of plasma triglycerides was highly varible; the mean for each group was elevated by the drug. Colestipol was well-tolerated and its effect did not diminish with time. It is a useful drug in the treatment of hypercholesterolemia.

Influence of bezafibrate and colestipol on LDL-cholesterol, LDL-apolipoprotein B and HDL-cholesterol in hyperlipoproteinaemia.

A significant increase of LDL-apolipoprotein B by 13% and LDL-cholesterol by 19% was observed in a group of 9 patients with hyperlipoproteinaemia Type III after bezafibrate treatment. Additional administration of colestipol caused a significant decrease of both LDL-apolipoprotein B by 18% and LDL-cholesterol by 25%. In 10 patients of hyperlipoproteinaemia Type IIb a significant decrease of both LDL-apolipoprotein B by 28% and LDL-apolipoprotein B by 18% was observed after bezafibrate therapy. When bezafibrate was given together with colestipol a further decrease of both LDL-cholesterol by 17% and LDL-apolipoprotein B by 16% occurred. HDL-cholesterol concentration increased significantly in both groups of hyperlipaemic patients during therapy. This may be the effect of both bezafibrate and colestipol. It is concluded that bile acid resins may effectively prevent the LDL-cholesterol concentration increase observed sometimes after clofibrate analogues.

Enhanced low-density lipoprotein cholesterol reduction and cost-effectiveness by low-dose colestipol plus lovastatin combination therapy.

A total of 96 patients with moderate elevations of low-density lipoprotein (LDL) cholesterol were randomly assigned to 4 different double-blind treatment regimens: placebo; colestipol 5 g and lovastatin 20 mg/day (C5 + L20); colestipol 10 g and lovastatin 20 mg/day (C10 + L20); and lovastatin 40 mg/day (L40). During 12 weeks of therapy, C10 + L20 achieved the greatest reduction in total cholesterol (-32%) and LDL cholesterol (-48%) levels from baseline. This combination also exhibited significantly greater reductions in LDL cholesterol levels than the C5 + L20 and L40 groups (p < 0.01). The differences in total and LDL cholesterol reduction between the C5 + L20 and L40 groups were not significant. Similar changes and differences between treatments were seen in apolipoprotein B levels. Whereas mean total apolipoprotein A-I levels increased with all treatments (p < 0.05), lipoprotein particles A-I were significantly increased in the C10 + L20 group (p < 0.01) only. Results demonstrate that the combination of low-dose lovastatin (20 mg/day) with low-dose colestipol (5 or 10 g/day) produces LDL cholesterol reductions equal to or greater than higher doses of lovastatin (40 mg/day). In addition, low-dose combinations are > 25% more cost-effective than high-dose monotherapy.

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.

Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia.

Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Use of niacin, statins, and resins in patients with combined hyperlipidemia.

Patients in the original Familial Atherosclerosis Treatment Study (FATS) cohort were subgrouped into those with triglyceride levels < or = 120 mg/dL (n = 26) and those with triglyceride levels > or = 190 mg/dL (n = 40). Their therapeutic responses to niacin plus colestipol, lovastatin plus colestipol, colestipol alone, or placebo were determined. Therapeutic response was also determined in the same 2 triglyceride subgroups (n = 12 and n = 27, respectively) of patients selected for low levels of high-density lipoprotein (HDL) cholesterol and coronary artery disease. These triglyceride criteria were chosen to identify patient subgroups with high likelihood of "pattern A" (normal-size low-density lipoprotein [LDL] particles and triglyceride < or = 120 mg/dL) or "pattern B" (small dense LDL and triglyceride > or = 190 mg/dL). Our findings in these small patient subgroups are consistent with the emerging understanding that coronary artery disease patients presenting with high triglyceride levels have lower HDL-C, smaller less buoyant LDL-C, and greater very low-density lipoprotein (VLDL) cholesterol and VLDL apolipoprotein B, and are more responsive to therapy as assessed by an increase in HDL-C and reduction in triglycerides, VLDL-C, and VLDL apolipoprotein B. In the FATS high-triglyceride subgroup with these characteristics, a tendency toward greater therapeutic improvement in coronary stenosis severity was observed among those treated with either of the 2 forms of intensive cholesterol-lowering therapy. This improvement is associated with therapeutic reduction of LDL-C and elevation of HDL-C, but also appears to be associated with drug-induced improvement in LDL buoyancy.

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.

Colestipol: a review of its pharmacological properties and therapeutic efficacy in patients with hypercholesterolaemia.

Colestipol is an anion exchange resin with bile acid sequestering properties resembling those of cholestyramine, another lipid-lowering binding resin. In daily doses of 15 to 30g colestipol reduces total plasma cholesterol concentrations (primarily low density lipoprotein cholesterol) by about 15 to 30%, but plasma triglyceride concentrations may be unchanged or in some patients increased. Thus, like cholestyramine, colestipol is of benefit in patients with primary hypercholesterolaemia without associated hypertriglyceridaemia (type IIa hyperlipoproteinaemia). Colestipol is odourless and tasteless, and is said by some to be more readily tolerated by patients than cholestyramine, leading to improved compliance, but such data has not been documented in most studies. Side effects of colestipol treatment are primarily gastrointestinal in nature since the drug is essentially unabsorbed. As with cholestyramine, colestipol may bind with other concomitantly administered drugs reducing their absorption or enterohepatic recirculation; dosage intervals of other concurrent medications should be adjusted to minimise the potential for such an interaction.

Primary hypercholesterolemia: effect of treatment on serum lipids, lipoprotein fractions, cholesterol absorption, sterol balance, and platelet aggregation.

The nonabsorbable bile acid sequestrant resin, colestipol, was administered to 16 patients with primary hypercholesterolemia, and its effect on serum lipids, lipoprotein fractions, and circulating platelet aggregate ratio and platelet aggregation in response to adenosine diphosphate (ADP) was compared with that of sitosterol. Cholesterol absorption and sterol balance studies were done in four of the subjects during the following treatment periods: diet alone, colestipol, and sitosterol. Total serum cholesterol was significantly reduced by colestipol but only slightly decreased by sitosterol. Combination treatment with colestipol and sitosterol was associated with a smaller decrease in serum cholesterol than was demonstrated with colestipol alone. Serum triglycerides tended to increase during colestipol therapy (this increase was not clinically significant) but showed a minimal nonsignificant decrease with sitosterol treatment. Colestipol decreased cholesterol absorption, whereas sitosterol slightly increased it. Fecal sterol excretion was increased with colestipol treatment but was minimally affected by administration of sitosterol. Low-density lipoprotein and high-density lipoprotein cholesterol significantly decreased with colestipol treatment. The circulating platelet aggregate ratio was significantly lower in the group of patients with hypercholesterolemia who received colestipol initially than in control subjects, but platelet aggregation in response to ADP was not significantly different between these two groups. No significant change in platelet aggregation was noted during colestipol or sitosterol treatment despite a significant decrease in total serum cholesterol with colestipol therapy, a suggestion that the platelet and lipid abnormalities are not interrelated.

The effect of colestipol dose on postprandial serum bile acid concentration: assessment by an enzymic bioluminescence procedure.

A dose-response study was performed with three doses of colestipol, using postprandial serum bile acid levels to assess bile acid sequestering activity in 40 volunteers with asymptomatic hyperlipidaemia. Subjects who entered the study had total serum cholesterol concentrations greater than 220 mg/dl and triglyceride concentrations less than 200 mg/dl. They were randomly assigned to one of four parallel treatment groups: (a) placebo b.d., (b) colestipol (as Colestid hydrochloride granules) 2.5 g b.d., (c) colestipol 5 g b.d., and (d) colestipol 7.5 g b.d. Subjects were maintained on a constant repeating solid diet throughout the 6-day study period, and colestipol was ingested 30 min before breakfast and dinner. No drug was administered on Days 1-3; baseline (pre-treatment) serum bile acid concentration profiles were determined on Day 3. The above treatments were given on Days 4-6, and total serum bile acid concentrations were determined at 30- or 60-min intervals for 10 h on Days 4 and 6. Serum bile acids were measured using a bioluminescence procedure which enzymically measures total 3 alpha hydroxy bile acids. Serum bile acid concentrations were significantly decreased from the pretreatment period by 5.0 and 7.5 g/day as compared to 2.5 g/day or placebo. Differences from the pre-treatment period in the area under the serum bile acid time curve revealed the same trends in the data as analysis of percentage difference (Day 6 vs pre-treatment period) in serum bile acid concentrations. These results indicate that postprandial serum bile acid concentrations are influenced by colestipol in a dose-related manner, with doses of 5 and 7.5 g b.d. having a significantly greater effect than 2.5 g b.d. The dose of 7.5 g b.d. had an identical effect on serum bile acid patterns as a dose of 5.0 g t.d.s., which was previously reported. Our findings also show that changes in serum bile acid concentrations may be used to follow the immediate effects of bile acid sequestration in hypercholes terolaemic subjects, and that the bioluminescence enzyme technique is sufficiently sensitive to detect such changes.