Colesevelam hydrochloride: a novel bile acid-binding resin.
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of colesevelam hydrochloride, a bile acid-binding resin.


METHODS
MEDLINE searches (1966-June 2000) and manufacturer prescribing literature were employed to find articles on colesevelam. Additional studies and abstracts were identified from the bibliographies of reviewed literature.


METHODS
All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Priority was given to randomized, double-blind, placebo-controlled studies.


RESULTS
Colesevelam HCl is a nonabsorbed hydrogel with bile acid sequestrant properties. Monotherapy using colesevelam in once-daily or two divided daily doses of 1.5-4.5 g has produced significant reductions in total cholesterol and low-density lipoprotein (LDL) cholesterol. Mean LDL cholesterol decreases to 20% have been noted when the patient is on 3.75-4.5 g/d. Increases in high-density lipoprotein (HDL) cholesterol have been observed (up to 9%), whereas triglycerides (TG) have increased significantly to 25% in some studies. In unpublished studies, combined use of colesevelam plus hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor have produced greater reductions in LDL cholesterol than either the statin or colesevelam administered alone. The efficacy of colesevelam monotherapy is slightly less than or similar to cholestyramine or colestipol in decreasing LDL cholesterol, although colesevelam is more potent on a gram-to-gram basis. Adverse effects have been minimal with colesevelam in published studies; this suggests an advantage over cholestyramine or colestipol therapy. Colesevelam appears to be more cost-effective than the packet dosage form of the brand formulation of the older bile acid resins. Care in selection of an appropriate agent should be exercised when considering the issues of adverse effects and palatability.


CONCLUSIONS
Colesevelam alone or combined with an HMG-CoA reductase inhibitor is effective in the reduction of total and LDL cholesterol. Since colesevelam is formulated as a tablet, problems with palatability such as with the powder formulation of the bile acid-binding resins are likely to be eliminated.
Aldridge
M A
MA
School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, USA.
Ito
M K
MK
D000328:Adult; D000368:Aged; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D002352:Carrier Proteins / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D000499:Allylamine; D000924:Anticholesteremic Agents; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)