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Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin.
Curr Med Res Opin. 2004 Jun; 20(6):955-65.CM

Abstract

BACKGROUND

Ezetimibe is a cholesterol absorption inhibitor which decreases low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. This study investigated the potential for pharmacodynamic and/or pharmacokinetic interactions between ezetimibe and lovastatin.

METHODS

In a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study, 48 healthy men with hypercholesterolemia (screening LDL-C >or= 130 mg/dL) who were stabilized and maintained on a National Cholesterol Education Program (NCEP) Step I diet were randomized to one of the following six oral treatments once daily for 14 days: lovastatin 20 mg; lovastatin 20 mg plus ezetimibe 5, 10, or 20 mg; lovastatin 40 mg plus ezetimibe 10mg; or placebo.

RESULTS

Reported adverse events were generally mild, nonspecific, and similar among treatments. There were no significant changes in safety laboratory test results, including those for enzymes indicative of muscle or liver injury. Coadministration of ezetimibe and lovastatin did not increase the plasma concentrations of lovastatin or beta-hydroxylovastatin. In this parallel comparison study there was an apparent decrease in lovastatin exposure, however, the reduction in lovastatin or beta-hydroxylovastatin concentrations was not related to the ezetimibe dose and is not considered to be clinically important. Ezetimibe 5, 10, or 20 mg combined with lovastatin 20 mg caused a significantly (p < 0.01) greater reduction in LDL-C than lovastatin 20 mg alone, with no apparent effect on HDL-C or triglycerides. LDL-C was reduced by 51.0% with ezetimibe 10 mg plus lovastatin 20 mg, 56.0% with ezetimibe 10 mg plus lovastatin 40 mg, 33.2% with lovastatin alone, and 17.3% with placebo.

CONCLUSIONS

The co-administration of ezetimibe and lovastatin was well tolerated and resulted in a significantly greater percentage reduction in serum LDL-C concentrations than with lovastatin alone, with an average incremental reduction of 16-18%. Ezetimibe 10mg appears to be the optimal dose when co-administered with lovastatin 20mg once daily. Further incremental reductions in LDL-C from the co-administration of ezetimibe and lovastatin are expected only when the dose of lovastatin is increased. The co-administration of ezetimibe and lovastatin has the potential to produce clinically significant reductions in LDL-C compared to either drug alone, with favorable safety and tolerability.

Authors+Show Affiliations

Department of Early Clinical Research & Experimental Medicine, Schering-Plough Research Institute, Kenilworth, NJ 07033-1300, USA. teddy.kosoglou@spcorp.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15200755

Citation

Kosoglou, Teddy, et al. "Effects of Ezetimibe On the Pharmacodynamics and Pharmacokinetics of Lovastatin." Current Medical Research and Opinion, vol. 20, no. 6, 2004, pp. 955-65.
Kosoglou T, Statkevich P, Meyer I, et al. Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. Curr Med Res Opin. 2004;20(6):955-65.
Kosoglou, T., Statkevich, P., Meyer, I., Cutler, D. L., Musiol, B., Yang, B., Zhu, Y., Maxwell, S. E., & Veltri, E. P. (2004). Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. Current Medical Research and Opinion, 20(6), 955-65.
Kosoglou T, et al. Effects of Ezetimibe On the Pharmacodynamics and Pharmacokinetics of Lovastatin. Curr Med Res Opin. 2004;20(6):955-65. PubMed PMID: 15200755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. AU - Kosoglou,Teddy, AU - Statkevich,Paul, AU - Meyer,Ingo, AU - Cutler,David L, AU - Musiol,Bernhard, AU - Yang,Bo, AU - Zhu,Yali, AU - Maxwell,Stephen E, AU - Veltri,Enrico P, PY - 2004/6/18/pubmed PY - 2004/9/24/medline PY - 2004/6/18/entrez SP - 955 EP - 65 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 20 IS - 6 N2 - BACKGROUND: Ezetimibe is a cholesterol absorption inhibitor which decreases low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. This study investigated the potential for pharmacodynamic and/or pharmacokinetic interactions between ezetimibe and lovastatin. METHODS: In a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study, 48 healthy men with hypercholesterolemia (screening LDL-C >or= 130 mg/dL) who were stabilized and maintained on a National Cholesterol Education Program (NCEP) Step I diet were randomized to one of the following six oral treatments once daily for 14 days: lovastatin 20 mg; lovastatin 20 mg plus ezetimibe 5, 10, or 20 mg; lovastatin 40 mg plus ezetimibe 10mg; or placebo. RESULTS: Reported adverse events were generally mild, nonspecific, and similar among treatments. There were no significant changes in safety laboratory test results, including those for enzymes indicative of muscle or liver injury. Coadministration of ezetimibe and lovastatin did not increase the plasma concentrations of lovastatin or beta-hydroxylovastatin. In this parallel comparison study there was an apparent decrease in lovastatin exposure, however, the reduction in lovastatin or beta-hydroxylovastatin concentrations was not related to the ezetimibe dose and is not considered to be clinically important. Ezetimibe 5, 10, or 20 mg combined with lovastatin 20 mg caused a significantly (p < 0.01) greater reduction in LDL-C than lovastatin 20 mg alone, with no apparent effect on HDL-C or triglycerides. LDL-C was reduced by 51.0% with ezetimibe 10 mg plus lovastatin 20 mg, 56.0% with ezetimibe 10 mg plus lovastatin 40 mg, 33.2% with lovastatin alone, and 17.3% with placebo. CONCLUSIONS: The co-administration of ezetimibe and lovastatin was well tolerated and resulted in a significantly greater percentage reduction in serum LDL-C concentrations than with lovastatin alone, with an average incremental reduction of 16-18%. Ezetimibe 10mg appears to be the optimal dose when co-administered with lovastatin 20mg once daily. Further incremental reductions in LDL-C from the co-administration of ezetimibe and lovastatin are expected only when the dose of lovastatin is increased. The co-administration of ezetimibe and lovastatin has the potential to produce clinically significant reductions in LDL-C compared to either drug alone, with favorable safety and tolerability. SN - 0300-7995 UR - https://www.unboundmedicine.com/medline/citation/15200755/Effects_of_ezetimibe_on_the_pharmacodynamics_and_pharmacokinetics_of_lovastatin_ L2 - https://www.tandfonline.com/doi/full/10.1185/030079904125003872 DB - PRIME DP - Unbound Medicine ER -