The DOI matches its Crossref record; 49 of the 52 references it cites were found in a registry or an index.
Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin
Open accessAbstract
Aims The primary aims of these two single‐centre, randomized, evaluator‐blind, placebo/positive‐controlled, parallel‐group studies were to evaluate the potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe 0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation of the tolerance of the coadministration of ezetimibe and simvastatin was a secondary objective. Methods Eighty‐two healthy men with low‐density lipoprotein cholesterol (LDL‐C) ≥130 mg dl−1 received study drug once daily in the morning for 14 days. In Study 1 (n=58), five groups of 11–12 subjects received simvastatin 10 mg alone, or with ezetimibe 0.25, 1, or 10 mg or placebo. In Study 2 (n=24), three groups of eight subjects received simvastatin 20 mg alone, ezetimibe 10 mg alone, or the combination. Blood samples were collected to measure serum lipids in both studies. Steady‐state pharmacokinetics of simvastatin and its β‐hydroxy metabolite were evaluated in Study 1 only. Results In both studies, reported side‐effects were generally mild, nonspecific, and similar among treatment groups. In Study 1, there were no indications of pharmacokinetic interactions between simvastatin and ezetimibe. All active treatments caused statistically significant (P<0.01) decreases in LDL‐C concentration vs placebo from baseline to day 14. The coadministration of ezetimibe and simvastatin caused a dose‐dependent reduction in LDL‐C and total cholesterol, with no apparent effect on high‐density lipoprotein cholesterol (HDL‐C) or triglycerides. The coadministration of ezetimibe 10 mg and simvastatin 10 mg or 20 mg caused a statistically (P<0.01) greater percentage reduction (mean −17%, 95% CI −27.7, −6.2, and −18%, −28.4, −7.4, respectively) in LDL‐C than simvastatin alone. Conclusions The coadministration of ezetimibe at doses up to 10 mg with simvastatin 10 or 20 mg daily was well tolerated and caused a significant additive reduction in LDL‐C compared with simvastatin alone. Additional clinical studies to assess the efficacy and safety of coadministration of ezetimibe and simvastatin are warranted.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Ezetimibe selectively inhibits the absorption of cholesterol in the small intestine [by interfering with the Niemann-Pick C1-like 1 protein (NPC1L1)] without modifying uptake of other nutrients and vitamins [56, 57].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [56]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Ezetimibe targets the Niemann-Pick C1-like 1 (NPC1L1) protein, thereby reducing absorption of cholesterol from the intestine.15,16”
From Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (2015) · cites this paper as [16]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
OLSSON, A. G., McMurray, J. J. V., Thorgeirsson, G., Spaulding, C. M., Slattery, J., Pyörälà, K., Færgeman, O., Wright, R. S., Berg, K. M., Wilhelmsen, L., et al. (1994) · The Lancet · Cited by 8,467
Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511163332001 · Cited by 7,449
Sacks, F. M., Pfeffer, M. A., Moye, L. A., Rouleau, J. L., Rutherford, J. D., Cole, T. G., Brown, L., Warnica, J. W., Arnold, J. M. O., Wun, C.-C., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610033351401 · Cited by 7,439
(1998) · New England Journal of Medicine · doi:10.1056/nejm199811053391902 · Cited by 5,261
Downs, J. R., Clearfield, M., Weis, S., Whitney, E., Shapiro, D. R., Beere, P. A., Langendorfer, A., Stein, E. A., Kruyer, W., Gotto, Jr., et al. (1998) · JAMA · doi:10.1001/jama.279.20.1615 · Cited by 5,236
Gibaldi, M., & Perrier, D. G. (1982) · CRC Press eBooks · doi:10.1201/b14095 · Cited by 4,093
SCANDINAVIANSIMVASTATINSURVIVAL (1994) · The Lancet · doi:10.1016/s0140-6736(94)90566-5 · Cited by 3,638
PREVENTION OF CORONARY HEART DISEASE WITH PRAVASTATIN IN MEN WITH HYPERCHOLESTEROLEMIA
Hepherd, J. A. S., Obbe, S. T. M. C., Ord, I. A. F., Sles, C. H. G. I., Orimer, A. R. O. L., Acfarlane, P. E. W. M., Illop, J. A. H. M. C. K., Ackard, C. H. J. P., & Roup, S. T. G. (1995) · Cited by 3,453
Pedersen, T. R. (2004) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2004.08.027 · Cited by 3,098
Research works printed but not linked: 5
- Zhu Y, 2000, Effect of ezetimibe (SCH 58235) on the activity of drug metabolizing enzymes in vivo, Clin Pharmacol Ther, 67, 152
- Zhu Y, 2000, Pharmacokinetics of ezetimibe in rats, dogs, and humans, AAPS Pharm Sci Supplement, 2, 2660
- Kosoglou T, 2001, Multiple‐dose safety and pharmacokinetics of ezetimibe in adolescent children, Clin Pharmacol Ther, 69, P52
- Kosoglou T, 2001, Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and atorvastatin, J Am Coll Cardiol, 37, 229A
- 10.1111/j.1525-1373.2000.22524.x · DOI
Cited by
Sorted by citations
Items 101–117 of 117
Management of Chronic Coronary Artery Disease
Thomas, S., & Boden, W. E. (2012) · Wiley eBooks · doi:10.1002/9781118399378.ch3
Efficacy and Safety in Clinical Trials
Cohn, J. N. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.11.015
Atlee, W. C., Vasudevan, M., & Ubaidulla, U. (2013)
T RATAMIENTO D E L AS H IPERLIPEMIAS EN P ACIENTES C ON R IESGO C ARDIOVASCULAR E LEVADO
Padial, L. R., López, J. A., & Salicio, E. R. (2006)
Cardiovascular Clinical Trials
(2012) · Wiley eBooks · doi:10.1002/9781118399378
Management of Elevated Low-Density Lipoprotein Cholesterol
Davidson, M. H., & Robinson, J. G. (2013) · CRC Press eBooks · doi:10.3109/9781420019667-13
Tocotrienols in Hyperlipidemic Conditions
Minhajuddin, M., & Iqbal, J. (2008) · CRC Press eBooks · doi:10.1201/9781420080391.ch20
Drugs that affect lipid metabolism
Ohashi, W., & Hattori, Y. (2014) · Side effects of drugs annual · doi:10.1016/b978-0-444-62635-6.00044-9
de Oliveira, P. R. (2007) · Americanae (AECID Library)
Emerging Lipid-Lowering Therapies in Secondary Prevention
Mahtta, D., Virani, S. S., & Bavry, A. A. (2019) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-019-0607-z
Novel Therapies for Dyslipidemia
Tafaj-Reddy, O. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88477
Management of Elevated Low-Density Lipoprotein Cholesterol
Davidson, M. H., & Robinson, J. G. (2006) · Fundamental and clinical cardiology · doi:10.3109/9781420019667.007
Cada, D. J., Levien, T. L., & Baker, D. E. (2004) · Hospital Pharmacy · doi:10.1177/001857870403901109
Bartsch, F., Grzegorzewski, J., Pujol, H. L., Tautenhahn, H., & König, M. (2023) · medRxiv · doi:10.1101/2023.02.01.23285358
Morse, B. L., Han, B., Alberts, J. J., Posada, M. M., Dickinson, G. L., & Hall, S. D. (2026) · The AAPS Journal · doi:10.1208/s12248-026-01299-8
Metadata
- Authors
- Kosoglou, T., Meyer, I., Veltri, E. P., Statkevich, P., Yang, B., Zhu, Y., Mellars, L., Maxwell, S. E., Patrick, J. E., Cutler, D. L., Batra, V. K., & Affrime, M. B.
- Affiliations
- IQVIA (United States) (US)
- Corresponding author
- Kosoglou, Teddy
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2002-09
- Volume
- 54
- Issue
- 3
- Pages
- 309-319
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1874429
- OpenAlex
- W1498903994
- Semantic Scholar
- 72c4048e09bae02d9558d6f422ca2effd4944f2f
- Cited by
- 117
- References
- 52
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2020: 3 · 2019: 6 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 4
- FWCI
- 14.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- ezetimibe, simvastatin, drug-drug interactions, pharmacodynamic interactions, pharmacokinetic interactions, LDL cholesterol, total cholesterol, statins, cholesterol absorption inhibitors, serum lipids, hypercholesterolemia, dose dependence, healthy men, healthy women, healthy children, healthy older adults, healthy pregnant women
- MeSH terms
- Ezetimibe, Administration, Oral, Adult, Anticholesteremic Agents, Azetidines, Biological Availability, Dose-Response Relationship, Drug, Drug Combinations, Drug Interactions, Humans, Cholesterol, LDL, Male, Middle Aged, Body Mass Index, Simvastatin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
