Effect of Colesevelam on Lovastatin Pharmacokinetics

Donovan, Joanne M.; Kisicki, James C.; Stiles, Mark R.; Tracewell, William; Burke, Steven K.

doi:10.1345/aph.1a144

Cited by 21 publications

(17 citation statements)

References 40 publications

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“…[40][41][42] No significant interaction has been shown during colesevelam and fenofibrate co-administration or after a 4-hour dosing interval. 43 Although studies have not evaluated any interaction between colesevelam and ezetimibe, significant further reduction in LDL-c levels occurs with combined colesevelamezetimibe therapy.…”

Section: Drug-drug Interactionmentioning

confidence: 97%

Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

2010

Clinical Medicine Reviews in Vascular Health

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Background: Statins are recommended as first line therapy for the prevention of cardiovascular disease. Some individuals are statin intolerant or may need additional cholesterol lowering to achieve their cholesterol targets. Purpose: To review the pharmacology, clinical efficacy and safety of colesevelam mono-and combination therapy in patients with hypercholesterolemia. Data source: English-language journals from PUBMED MEDLINE (without restriction of date) using key word colesevelam. Results: Trials of colesevelam as monotherpy or in combination had baseline LDL-c levels of 130 to 202 mg/dl and triglycerides levels of 114 to 230 mg/dl. Colesevelam monotherapy reduced LDL-c by 9%-20% while increasing triglycerides 6%-25%. When added to low or moderate dose statin therapy, colesevelam decreased LDL-c an additional 6%-16%; when added to fenofibrate, colesevelam additionally decreased LDL-c by 17% and non-HDL-c by 7%; and when added to statin + niacin 2 gr additionally decreased LDL-c by 10%. The hypertriglyceridemia observed with colesevelam monotherapy was largely attenuated when colesevelam was coadministered with statins, fenofibrate, or niacin 2 gr. Coadministration of colesevelam with ezetimibe provided variable additional LDL-c reductions ranging from 0 to 20% over ezetimibe alone, and triglyceride responses were similarly variable. In diabetic individuals with modest hypertriglyceridemia, colesevelam reduced hemoglobin A1c by 0.5%. Colesevelam has fewer drug interactions than older bile acid sequestrants and is well-tolerated when used in combination with other lipid-lowering medications as well as with oral anti-diabetes medications or insulin. Conclusion: Colesevelam is an option for patients who have not achieved their LDL-c and non-HDL-c goals with statin therapy, or who are statin intolerant. Colesevelam is also an option to lower both LDL-c and glucose levels in patients with inadequately controlled diabetes.

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Section: Drug-drug Interactionmentioning

confidence: 97%

Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

2010

Clinical Medicine Reviews in Vascular Health

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“…Colesevelam has a synergistic effect in lowering LDL when used in conjunction with statins [10], which offers further treatment options for patients who are on maximum doses of statins and have not achieved target LDL levels. Importantly, colesevelam does not affect the pharmacokinetics or absorption of statins, so the two drugs can be used in combination without adjusting the schedule or dosing of the statin [11]. Combination studies with colesevelam and modest doses of simvastatin have demonstrated a 40% reduction in LDL cholesterol levels with a concomitant decrease in apoB-100 being greater than with either colesevelam or simvastatin alone [12•].…”

Section: Colesevelammentioning

confidence: 99%

Hypolipidemic therapy and cholesterol absorption

Manhas

Farmer

2004

Curr Atheroscler Rep

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The advent of safe and effective hypolipidemic therapy has revolutionized the ability of the clinician to optimize abnormalities in the lipid profile. The advent of statin therapy has provided a potent option to decrease low-density lipoprotein and frequently allows achievement of National Cholesterol Education Program target lipid levels with monotherapy. However, lipid goals are frequently not achieved due to inadequate response to therapy or side effects. The role of combination therapy in the optimization of the lipid profile provides a means by which the implementation of pharmacologic agents with synergistic mechanisms of action allows further improvement in circulating levels of low-density lipoprotein cholesterol. Statins have been combined with bile acid resins, fibric acid derivatives, and nicotinic acid. However, bile acid resins, although not systemically absorbed, have significant problems with patient compliance and drug interactions. The implementation of therapy with fibric acid derivatives or nicotinic acid increases the risk of significant side effects such as rhabdomyolysis or liver toxicity. Ezetimibe is a prototype of a new class of agents that specifically block the absorption of cholesterol from the gastrointestinal tract. Ezetimibe has minimal systemic absorption and a metabolic pathway involving enterohepatic circulation that allows for once a day administration due to a prolonged half-life. Ezetimibe lacks the drug interactions that are common with the bile acid resins and it may be utilized as either monotherapy or in combination with other pharmacologic agents. Ezetimibe has a relatively flat dose-response curve and titration is not required. This review centers on the role of pharmacologic agents that act predominantly by the reduction of cholesterol absorption, including colesevelam and ezetimibe.

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“…The literature has reported drug-drug interactions between lovastatin and drugs or related products with effect on drugs such as colesevelam, gemfibrozil, itraconazole or dietary supplements determined via pharmacokinetic studies [10][11][12][13][14][15]. Berberine is an alkaloid available from the medicinal plant Coptis chinensis that is widely used clinically in the treatment of gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia.…”

Section: Introductionmentioning

confidence: 99%

“…In the in vitro HepG2 cells experiments, berberine could increase the metabolic activity by increasing the metabolic parameters of CL, which was increased from 1.06 to 1.48 mL/10 5 (cell)·h −1 with the induction of berberine, the Km was increased three times in berberine induced group as well, which was compliance with the obtained pharmacokinetics parameter from AUC0-12 of lovastatin decreased 2.5 times (approximately three times). The literature has reported drug-drug interactions between lovastatin and drugs or related products with effect on drugs such as colesevelam, gemfibrozil, itraconazole or dietary supplements determined via pharmacokinetic studies [10][11][12][13][14][15]. Berberine is an alkaloid available from the medicinal plant Coptis chinensis that is widely used clinically in the treatment of gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia.…”

Section: Introductionmentioning

confidence: 99%

In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies

et al. 2016

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Background:We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. Methods: An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and berberine. SD male rats were random divided into lovastatin group and berberine induced prior to lovastatin group for the in vivo pharmacokinetic studies. Meanwhile HepG2 cells were induced by berberine for three days to study the metabolism of lovastatin. Results: The AUC (p < 0.01) and C max (p < 0.01) could be significantly decreased in the berberine-induced group in vivo, and the metabolic activity of HepG2 cell ccould be increased by berberine induction in vitro. The metabolism parameters of lovastatin such as CL, V max and K m were increased after the induction of berberine. From the pharmacokinetic study of lovastatin induced with berberine, we obtained pharmacokinetic parameters which are compliance with the metabolic parameters of lovastatin in HepG2 cells with berberine induction in vitro. Conclusions: From the in vivo pharmacokinetics study and the HepG2 cell metabolism study in vitro, berberine could be an inducer for the metabolism of lovastatin according to our previous research on berberine induction effects on HepG2 cells, which may be relevant to the fact that berberine possesses induction effects through the CYP 450 3A4 enzyme.

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Effect of Colesevelam on Lovastatin Pharmacokinetics

Cited by 21 publications

References 40 publications

Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

Hypolipidemic therapy and cholesterol absorption

In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies

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