Colesevelam: Potential Uses for the Newest Bile Resin

Abstract

Colesevelam is the newest bile resin with a unique chemical structure. It binds to bile acids with higher affinity than traditional bile acid sequestrants and has fewer gastrointestinal side effects and drug interactions. Colesevelam is safe and efficacious alone or in combination with HMG-CoA reductase inhibitors (statins) in reducing low-density lipoprotein cholesterol (LDL-C) levels. Despite this, the role of colesevelam in the treatment of hyperlipidemia remains limited, particularly in the face of new lipid lowering agents. As guidelines for cholesterol control become more stringent, the need to maximize therapeutic benefit through combination therapy will become increasingly more important. Colesevelam has a dose-sparing effect on statin therapy, potentially decreasing the risk of unwanted side effects or drug-drug interactions associated with statin use. This makes colesevelam a viable option for addition to a statin regimen when goal LDL-C levels cannot be achieved with a statin alone. Additionally, anecdotal reports indicate that colesevelam may have potential benefits in certain patient populations that cannot tolerate other lipid lowering therapies, including organ transplant recipients, cholestatic liver disesase, and end-stage renal disease. By recognizing the potential utility of colesevelam, clinicians can better manage those patients who are not able to tolerate first-line therapies.

Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

“…However, gastrointestinal side effects such as constipation, indigestion, dyspepsia, and flatulence are very common and together with the high doses required (15–30 g/day) adversely affect patient compliance and the efficacy of these agents. The recent development of a higher affinity bile acid binder Colesevelam decreased the required dose (Steinmetz and Schonder 2005), but the efficacy, patience compliance, and side effect profile still favors the use of statins as a first-line therapy. Based on its remarkable substrate specificity and expression on the intestinal brush border membrane, blocking the ASBT using high affinity, nonabsorbable inhibitors represented an attractive strategy and alternative to the sequestrants for treatment of hypercholesterolemia (Kramer and Glombik 2006).…”

Colesevelam for the management of Type 2 diabetes

“…The peak effects of colesevelam HCL on lipid parameters occur in the first 2 weeks of administration based on early reductions in LDL-C noted in clinical trials [46,47] . Davidson et al [48] demonstrated an LDL-C lowering effect of 19.1% after 6 weeks of administration with colesevelam HCL 3.75 g daily.…”

“…The maximum of [ 14 C] colesevelam HCL in whole blood was estimated to be 0.04% (0.17 ± 0.10 (µg Eq)/ml) at 72 h post dose. Colesevelam HCL has little to no volume of distribution, plasma protein binding, metabolism and renal clearance [27,46,47] .…”

Management of hyperlipidemias: An update

“…BASA promote apo-A1 synthesis by an unknown mechanism and tend to raise HDL levels. [44] Three BASA are currently available [ Table 3]. Their use has been hindered by inconvenient dosing and by unpleasant side effects (e.g., constipation).…”