Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records

Makoto Kakara, Hiroko Nomura, Masato Fukae, Keisuke Gotanda, Takeshi Hirota, Sunao Matsubayashi, Hideki Shimomura, Masaaki Hirakawa, Ichiro Ieiri

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

AIMS: HMG-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.

METHODS: Patient 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).

RESULTS: An 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.

CONCLUSIONS: A 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.

元の言語英語
ページ(範囲)824-835
ページ数12
ジャーナルBritish journal of clinical pharmacology
78
発行部数4
DOI
出版物ステータス出版済み - 10 1 2014

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Electronic Health Records
LDL Cholesterol
Population
Anticholesteremic Agents
Therapeutics
Pharmaceutical Preparations
Pharmacokinetics
Rosuvastatin Calcium
Ezetimibe

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

これを引用

Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records. / Kakara, Makoto; Nomura, Hiroko; Fukae, Masato; Gotanda, Keisuke; Hirota, Takeshi; Matsubayashi, Sunao; Shimomura, Hideki; Hirakawa, Masaaki; Ieiri, Ichiro.

:: British journal of clinical pharmacology, 巻 78, 番号 4, 01.10.2014, p. 824-835.

研究成果: ジャーナルへの寄稿記事

Kakara, Makoto ; Nomura, Hiroko ; Fukae, Masato ; Gotanda, Keisuke ; Hirota, Takeshi ; Matsubayashi, Sunao ; Shimomura, Hideki ; Hirakawa, Masaaki ; Ieiri, Ichiro. / Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records. :: British journal of clinical pharmacology. 2014 ; 巻 78, 番号 4. pp. 824-835.
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abstract = "AIMS: HMG-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.METHODS: Patient 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).RESULTS: An 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.CONCLUSIONS: A 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.",
author = "Makoto Kakara and Hiroko Nomura and Masato Fukae and Keisuke Gotanda and Takeshi Hirota and Sunao Matsubayashi and Hideki Shimomura and Masaaki Hirakawa and Ichiro Ieiri",
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T1 - Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records

AU - Kakara, Makoto

AU - Nomura, Hiroko

AU - Fukae, Masato

AU - Gotanda, Keisuke

AU - Hirota, Takeshi

AU - Matsubayashi, Sunao

AU - Shimomura, Hideki

AU - Hirakawa, Masaaki

AU - Ieiri, Ichiro

PY - 2014/10/1

Y1 - 2014/10/1

N2 - AIMS: HMG-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.METHODS: Patient 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).RESULTS: An 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.CONCLUSIONS: A 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.

AB - AIMS: HMG-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.METHODS: Patient 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).RESULTS: An 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.CONCLUSIONS: A 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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DO - 10.1111/bcp.12405

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SP - 824

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JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

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