ArticleBritish journal of clinical pharmacology2014
Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Pitavastatin effects on lipids in relation to major adverse cardiovascular events: a REPRIEVE secondary analysis.The lancet. HIV · 2026 · on this mapTrial
- Population Pharmacokinetics and Pharmacodynamics with Enterohepatic Recirculation of Co-Medication of Rosuvastatin and Ezetimibe.Drug design, development and therapy · 2025Trial
- Pharmacokinetic interactions and tolerability of rosuvastatin and ezetimibe: an open-label, randomized, multiple-dose, crossover study in healthy male volunteers.Drug design, development and therapy · 2018Trial
- Is there a role for earlier use of combination therapy?American journal of preventive cardiology · 2024Article
- Population pharmacokinetic and pharmacokinetic-pharmacodynamic modeling of bempedoic acid and low-density lipoprotein cholesterol in healthy subjects and patients with dyslipidemia.Journal of pharmacokinetics and pharmacodynamics · 2023Article
- Characterisation of individual ferritin response in patients receiving chelation therapy.British journal of clinical pharmacology · 2022Article
- Effects of Evolocumab Added to Moderate-Intensity Statin Therapy in Chinese Patients With Acute Coronary Syndrome: The EMSIACS Trial Study Protocol.Frontiers in physiology · 2021Article
- Development of a System for Postmarketing Population Pharmacokinetic and Pharmacodynamic Studies Using Real-World Data From Electronic Health Records.Clinical pharmacology and therapeutics · 2020Article
- The Adherence Rate Threshold is Drug Specific.Drugs in R&D · 2017Article
- Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe.Frontiers in pharmacology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsHMG-CoA reductase inhibitors are available for use in low density lipoprotein-cholesterol (LDL-C) lowering therapy. The purposes of this study were to develop a population pharmacodynamic (PPD) model to describe the time course for the LDL-C lowering effects of statins and assess the efficacy of combination therapy based on electronic medical records.
methodsPatient backgrounds, laboratory tests and prescribed drugs were collected retrospectively from electronic medical records. Patients who received atorvastatin, pitavastatin or rosuvastatin were enrolled. A physiological indirect response model was used to describe the changes observed in LDL-C concentrations. The PPD analysis was performed using nonmem 7.2.0 with the first order conditional estimation method with interaction (FOCE-INTER).
resultsAn indirect response Imax model, based on the 2863 LDL-C concentrations of 378 patients, successfully and quantitatively described the time course for the LDL-C lowering effects of three statins. The combination of ezetimibe, a cholesterol absorption inhibitor, decreased the LDL synthesis rate (Kin ) by 10.9%. A simulation indicated that the combined treatment of ezetimibe with rosuvastatin (2.5 mg day(-1) ) led to superior clinical responses than those with high doses of rosuvastatin (5.0 mg day(-1) ) monotherapy, even in patients with higher baseline LDL-C concentrations prior to the treatment.
conclusionsA newly constructed PPD model supported previous evidence for the beneficial effects of ezetimibe combined with rosuvastatin. In addition, the established framework is expected to be applicable to other drugs without pharmacokinetic data in clinical practice.
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