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The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe.
Curr Med Res Opin. 2005 Aug; 21(8):1171-9.CM

Abstract

OBJECTIVE

The objective of this study was to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and fluvastatin in healthy hypercholesterolemic subjects at clinically-relevant doses and to evaluate the potential for a pharmacokinetic drug interaction between ezetimibe and fluvastatin.

METHODS

In a single-center, evaluator-blind, placebo-controlled, multiple-dose, parallel-group study 32 healthy subjects with hypercholesterolemia were randomized to 4 treatments administered once daily for 14 days: ezetimibe 10 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe 10 mg, and ezetimibe placebo. Blood samples were collected to measure serum lipids and to determine steady-state pharmacokinetics.

RESULTS

Ezetimibe 10 mg significantly (p < or = 0.01) decreased total-cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations compared to placebo at Day 14. Fluvastatin 20 mg also caused a significant (p = 0.01) reduction in total-cholesterol and a decrease in LDL-C at Day 14 compared to placebo, however, the decrease in LDL-C did not reach statistical significance (p = 0.08). The coadministration of ezetimibe 10 mg and fluvastatin 20 mg caused significantly (p < or = 0.01) greater mean percent reductions in LDL-C and total-cholesterol than fluvastatin 20 mg alone or placebo at Day 14. Fluvastatin had no clinically significant effect on the pharmacokinetics of ezetimibe. On average, ezetimibe appeared to decrease the rate and extent of fluvastatin bioavailability.

CONCLUSION

Coadministration of ezetimibe and fluvastatin was safe and well tolerated and caused significant incremental reductions in LDL-C and total cholesterol compared to fluvastatin administered alone. The pharmacokinetics of ezetimibe were not affected by coadministration with fluvastatin. The apparent decrease in fluvastatin exposure on administration with ezetimibe was likely to be due to the parallel study design and two pharmacokinetic outliers and is considered of no clinical significance.

Authors+Show Affiliations

Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033-1300, USA. larisa.reyderman@spcorp.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16083526

Citation

Reyderman, Larisa, et al. "The Effect of Fluvastatin On the Pharmacokinetics and Pharmacodynamics of Ezetimibe." Current Medical Research and Opinion, vol. 21, no. 8, 2005, pp. 1171-9.
Reyderman L, Kosoglou T, Cutler DL, et al. The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe. Curr Med Res Opin. 2005;21(8):1171-9.
Reyderman, L., Kosoglou, T., Cutler, D. L., Maxwell, S., & Statkevich, P. (2005). The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe. Current Medical Research and Opinion, 21(8), 1171-9.
Reyderman L, et al. The Effect of Fluvastatin On the Pharmacokinetics and Pharmacodynamics of Ezetimibe. Curr Med Res Opin. 2005;21(8):1171-9. PubMed PMID: 16083526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe. AU - Reyderman,Larisa, AU - Kosoglou,Teddy, AU - Cutler,David L, AU - Maxwell,Stephen, AU - Statkevich,Paul, PY - 2005/8/9/pubmed PY - 2005/12/29/medline PY - 2005/8/9/entrez SP - 1171 EP - 9 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 21 IS - 8 N2 - OBJECTIVE: The objective of this study was to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and fluvastatin in healthy hypercholesterolemic subjects at clinically-relevant doses and to evaluate the potential for a pharmacokinetic drug interaction between ezetimibe and fluvastatin. METHODS: In a single-center, evaluator-blind, placebo-controlled, multiple-dose, parallel-group study 32 healthy subjects with hypercholesterolemia were randomized to 4 treatments administered once daily for 14 days: ezetimibe 10 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe 10 mg, and ezetimibe placebo. Blood samples were collected to measure serum lipids and to determine steady-state pharmacokinetics. RESULTS: Ezetimibe 10 mg significantly (p < or = 0.01) decreased total-cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations compared to placebo at Day 14. Fluvastatin 20 mg also caused a significant (p = 0.01) reduction in total-cholesterol and a decrease in LDL-C at Day 14 compared to placebo, however, the decrease in LDL-C did not reach statistical significance (p = 0.08). The coadministration of ezetimibe 10 mg and fluvastatin 20 mg caused significantly (p < or = 0.01) greater mean percent reductions in LDL-C and total-cholesterol than fluvastatin 20 mg alone or placebo at Day 14. Fluvastatin had no clinically significant effect on the pharmacokinetics of ezetimibe. On average, ezetimibe appeared to decrease the rate and extent of fluvastatin bioavailability. CONCLUSION: Coadministration of ezetimibe and fluvastatin was safe and well tolerated and caused significant incremental reductions in LDL-C and total cholesterol compared to fluvastatin administered alone. The pharmacokinetics of ezetimibe were not affected by coadministration with fluvastatin. The apparent decrease in fluvastatin exposure on administration with ezetimibe was likely to be due to the parallel study design and two pharmacokinetic outliers and is considered of no clinical significance. SN - 0300-7995 UR - https://www.unboundmedicine.com/medline/citation/16083526/The_effect_of_fluvastatin_on_the_pharmacokinetics_and_pharmacodynamics_of_ezetimibe_ L2 - https://www.tandfonline.com/doi/full/10.1185/030079905X46386 DB - PRIME DP - Unbound Medicine ER -