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Cited by 17Lipoproteins and Cardiovascular HealthPharmacogenetics and Drug MetabolismCancer, Lipids, and Metabolism

Consideraciones específicas en la prescripción e intercambio terapéutico de estatinas

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García-Sabina, A., Gulín-Dávila, J., Sempere-Serrano, P., González-Juanatey, C., Martínez-Pacheco, R.·2012·Farmacia Hospitalaria
DOI 10.1016/j.farma.2011.02.010
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Abstract

Actualmente existen seis estatinas comercializadas en España y una en proceso de comercialización. La elección de la más adecuada y de su dosis habitualmente viene determinada por el objetivo terapéutico; es decir, en el descenso de c-LDL. Se aceptan como dosis equivalentes de las distintas estatinas aquellas que consiguen el mismo porcentaje de descenso en c-LDL, sin embargo, se trata de fármacos que difieren no sólo en su potencia, sino también en sus propiedades farmacocinéticas. Una evaluación de las peculiaridades farmacocinéticas de cada estatina permite disponer de criterios para su elección, ayudando a determinar qué estatina puede ser más apropiada para un paciente en función de sus características individuales y de los medicamentos que son coadministrados. Se revisaron las características farmacocinéticas de cada estatina y las interacciones medicamentosas que de ello se derivan. El CYP3A4 es responsable del metabolismo de atorvastatina, simvastatina y lovastatina; el CYP2C9 de fluvastatina; la P-gp favorece la eliminación de atorvastina, pravastatina, simvastatina y lovastatina; y la actividad del transportador OATP1B1, que favorece el acceso al hepatocito de todas las estatinas excepto fluvastatina, es especialmente importante con rosuvastatina y pravastatina. Estas circunstancias son responsables de que aquellos fármacos que afectan a la actividad de estos isoenzimas o transportadores, bien por inhibición bien por inducción, no afecten por igual a la actividad de las diferentes estatinas. A la hora de seleccionar una estatina o de intercambiar una por otra, deben tomarse en consideración las características farmacocinéticas de cada una de ellas. The pharmaceutical industry currently offers six different statins in Spain and there is one more soon to be available. Choosing the most appropriate drug and dose is determined by the therapeutic target (reduction in LDL-C levels). Statin doses that decrease LDL-C at the same percentage are considered equivalent. Evaluating the pharmacokinetic characteristics of each statin can be useful when setting selection criteria, helping to determine which statin may be more appropriate for a patient based on their individual characteristics and on the other co-administered drugs. We reviewed the pharmacokinetics properties of each statin and its possible involvement in drug interactions. CYP3A4 was responsible for the metabolism of lovastatin, simvastatin and atorvastatin; fluvastatin depends on CYP2C9; P-glycoprotein is responsible for decreased atorvastatin, pravastatin, simvastatin and lovastatin concentrations. The OATPA1B1 transporter involved in all statins’ access to the hepatocyte, except for fluvastatin, is essential for rosuvastatin and pravastatin. These circumstances cause those drugs inhibiting or inducing isoenzymes or transporters’ activity not to have the same effect on the different statins. The pharmacokinetics is important when choosing the best statin and could be a limitation in the use of interchange therapeutic programmes when other drugs are present.

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  • Decreased fat accumulation likely occurs through the established effect of statins on liver LDL uptake.

    “Decreased fat accumulation likely occurs through the established effect of statins on liver LDL uptake38.”

    From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [38]

    The Introduction (page not provided) explains that statins increase LDL-receptor expression on hepatocytes, leading to greater removal of LDL cholesterol from the blood. It does not establish that this mechanism decreases fat accumulation; its separate mention of reduced cholesterol accumulation is not the same claim. (LLM, conf=0.86)

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  • Statin drugs regulate systemic cholesterol through two mechanisms: by inhibiting HMGCR and by modifying liver uptake of serum LDL and triglycerides.

    “Statin drugs regulate systemic cholesterol through two mechanisms: by inhibiting HMGCR and by modifying liver uptake of serum LDL and triglycerides38.”

    From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [38]

    The Introduction says statins inhibit HMG-CoA reductase and increase hepatocyte receptor expression, leading to greater removal of LDL cholesterol from circulating blood. It also says statins lower triglyceride levels, but does not describe this as increased liver uptake of triglycerides. (LLM, conf=0.88)

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Cited by

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Authors
García-Sabina, A., Gulín-Dávila, J., Sempere-Serrano, P., González-Juanatey, C., & Martínez-Pacheco, R.
Affiliations
Hospital Universitario Lucus Augusti (ES)
Corresponding author
García-Sabina, A.
Venue
Farmacia Hospitalaria
Publisher
Elsevier BV
Published
2012-03
Volume
36
Issue
2
Pages
97-108
ISSN
1130-6343 (ISSN-L)
DOI
10.1016/j.farma.2011.02.010
OpenAlex
W2133515739
Cited by
17
References
1
Citations by year
2026: 1 · 2025: 1 · 2022: 2 · 2021: 1 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 3 · 2013: 1 · 2012: 1
FWCI
0.12
Type
journal article
Language
es
Open access
Licence
Locations
  • Farmacia Hospitalaria (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Redalyc (Universidad Autónoma del Estado de México) (submittedVersion)
  • RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
statins, statin pharmacokinetics, statin selection, statin switching, drug interactions, CYP3A4, CYP2C9, P-glycoprotein, OATP1B1, LDL cholesterol lowering, atorvastatin, simvastatin, lovastatin, fluvastatin, pravastatin, rosuvastatin
MeSH terms
Anticholesteremic Agents, Aryl Hydrocarbon Hydroxylases, Drug Industry, Drug Interactions, Humans, Hypercholesterolemia, Liver, Drug Prescriptions, Spain, Hydroxymethylglutaryl-CoA Reductase Inhibitors, ATP Binding Cassette Transporter, Subfamily B, Member 1, Organic Anion Transporters, Liver-Specific Organic Anion Transporter 1, Cytochrome P-450 CYP2C9

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