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| __NOTOC__
| | #REDIRECT [[Colesevelam]] |
| {{Colesevelam}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Pharmacology==
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| ===Mechanism of Action===
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| Primary Hyperlipidemia: Colesevelam hydrochloride, the active pharmaceutical ingredient in WELCHOL, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. This causes an increased demand for cholesterol in the liver cells, resulting in the dual effect of increasing transcription and activity of the cholesterol biosynthetic enzyme, HMG-CoA reductase, and increasing the number of hepatic LDL receptors. These compensatory effects result in increased clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels. Serum TG levels may increase or remain unchanged.
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| Type 2 Diabetes Mellitus: The mechanism by which WELCHOL improves glycemic control is unknown.
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| ===Pharmacodynamics===
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| A maximum therapeutic response to the lipid-lowering effects of WELCHOL was achieved within 2 weeks and was maintained during long-term therapy. In the diabetes clinical studies, a therapeutic response to WELCHOL, as reflected by a reduction in hemoglobin A1C (A1C), was initially noted following 4-6 weeks of treatment and reached maximal or near-maximal effect after 12-18 weeks of treatment.
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| ===Pharmacokinetics===
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| '''Absorption''': Colesevelam hydrochloride is a hydrophilic, water-insoluble polymer that is not hydrolyzed by digestive enzymes and is not absorbed.
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| '''Distribution''': Colesevelam hydrochloride is not absorbed, and therefore, its distribution is limited to the gastrointestinal tract.
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| '''Metabolism''': Colesevelam hydrochloride is not metabolized systemically and does not interfere with systemic drug-metabolizing enzymes such as cytochrome P-450.
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| '''Excretion''': In 16 healthy volunteers, an average of 0.05% of administered radioactivity from a single 14C-labeled colesevelam hydrochloride dose was excreted in the urine.
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| '''Drug Interactions''': Drug interactions between colesevelam and concomitantly administered drugs were screened through in vitro studies and confirmed in in vivo studies.In vitro studies demonstrated that [[cephalexin]], [[metformin]], and [[ciprofloxacin]] had negligible binding to colesevelam hydrochloride. Therefore, an in vivo pharmacokinetic interaction of WELCHOL with these drugs is unlikely. WELCHOL was found to have no significant effect on the bioavailability of [[aspirin]], [[atenolol]], [[digoxin]], [[enalapril]], [[fenofibrate]], [[lovastatin]], [[metoprolol]],[[ phenytoin]],[[ pioglitazone]],[[ quinidine]],[[ rosiglitazone]], [[sitagliptin]],[[ valproic acid]], and [[warfarin]]. The results of additional in vivo drug interactions of WELCHOL are presented in Table 6.
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| |[[File:colesevelam06.jpg|thumb|800px]]
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| <small><small><small>a With verapamil, the dose of WELCHOL was 4.5 g</small></small></small>
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| <small><small><small>b Should be administered at least 4 hours prior to WELCHOL [See Drug Interactions (7)].</small></small></small>
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| <small><small><small>c Patients receiving concomitant metformin ER and colesevelam should be monitored for clinical response as is usual for the use of anti-diabetes drugs [See Drug Interactions (7)].</small></small></small>
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| <small><small><small>d Cyclosporine levels should be monitored and, based on theoretical grounds, cyclosporine should be administered at least 4 hours prior to WELCHOL [See Drug Interactions (7)].</small></small></small>
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| <small><small><small>* Oral contraceptive containing norethindrone and ethinyl estradiol.</small></small></small>
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| <small><small><small>N/A — Not Available</small></small></small><ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = WELCHOL (COLESEVELAM HYDROCHLORIDE) TABLET, FILM COATED WELCHOL (COLESEVELAM HYDROCHLORIDE) FOR SUSPENSION [DAIICHI SANKYO, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=4a06d3b2-7229-4398-baba-5d0a72f63821 | publisher = | date = | accessdate = 10 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| {{Lipid modifying agents}}
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| [[Category:Hepatology]]
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| [[Category:Bile acid sequestrants]]
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| [[Category:Cardiovasuclar Drugs]]
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| [[Category:Drugs]]
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