Influence of Cytochrome P450 2C19 Gene Variations on Pharmacokinetic Parameters of Thalidomide in Japanese Patients
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- Matsuzawa Naoki
- Department of Pharmacy, Shinshu University Hospital
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- Nakamura Katsunori
- Department of Pharmacy, Shinshu University Hospital
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- Matsuda Masayuki
- Department of Neurology and Rheumatology, Shinshu University Hospital
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- Ishida Fumihiro
- Division of Hematology, Department of Internal Medicine, Shinshu University School of Medicine
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- Ohmori Shigeru
- Department of Pharmacy, Shinshu University Hospital
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Purpose: Cytochrome P450 (CYP)2C19 polymorphisms may partly explain the variability of thalidomide concentration and adverse drug effects by altering its metabolism. To compare the genetic and clinical factors responsible for the adverse effects and efficacy of thalidomide treatment, we investigated CYP2C19 genetic polymorphisms in Japanese subjects. Materials and Methods: Variations in the CYP2C19 gene in 6 patients treated with thalidomide were analyzed. The dosage of thalidomide, concentrations of (R)- and (S)-thalidomide in whole blood, and clinical laboratory test results were used as pharmacokinetic and pharmacodynamic indices. Using genomic DNA, CYP2C19*2 and *3 allele frequencies were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Results: The frequencies of CYP2C19 PM and hetero EM (hetEM) genotypes in Japanese patients taking thalidomide were 2 (33.3%) and 4 (66.7%), respectively. The areas under the curve (AUC) of (R)-thalidomide were 3.42 and 5.33 μg·h/L, and those of (S)-thalidomide were 1.64 and 2.46 μg·h/L for hetEM and PM, respectively. Conclusions: This study provided new insights regarding the contribution of CYP2C19 gene variations to adverse responses to thalidomide. Genotyping of CYP2C19*2 and *3 can be considerably simplified by using KOD FX as a polymerase for prediction of adverse effects to thalidomide by the PCR-RFLP method. CYP2C19 PM patients tend to have high serum thalidomide concentrations.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 35 (3), 317-320, 2012
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679608259584
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- NII論文ID
- 130001872311
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC383nvVWhtw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 023439609
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- PubMed
- 22382316
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可