| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2021-01-05 |
| タイトル |
|
|
タイトル |
Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題 |
tolvaptan |
| キーワード |
|
|
主題 |
CYP3A5 |
| キーワード |
|
|
主題 |
pharmacokinetics |
| キーワード |
|
|
主題 |
ABCB1 |
| キーワード |
|
|
主題 |
4β-hydroxycholesterol |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 著者 |
Hoshikawa, Kohei
Naito, Takafumi
Akutsu, Shunta
Saotome, Masao
Maekawa, Yuichiro
Kawakami, Junichi
|
| 書誌情報 |
Basic & clinical pharmacology & toxicology
巻 126,
号 4,
p. 353-363,
発行日 2020-04
|
| 出版者 |
|
|
出版者 |
Wiley |
| 権利 |
|
|
権利情報 |
This is the peer reviewed version of the following article: "Basic & clinical pharmacology & toxicology" 126(4), 353-363, which has been published in final form at https://doi.org/10.1111/bcpt.13355. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Tolvaptan efficacy for heart failure has a large interindividual variation. This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients. Fifty-eight heart failure patients receiving oral tolvaptan for volume overload were enrolled. Blood samples for determination of predose plasma concentrations of tolvaptan and its metabolites were collected. CYP3A5 and ABCB1 genotypes, plasma 4β-hydroxycholesterol/total cholesterol ratio (4β-OHC/TC) and 25-hydroxyvitamin D (25-OHD), and serum laboratory test values were evaluated. The CYP3A5*3/*3 genotype was associated with a higher plasma concentration of tolvaptan but not with its metabolic ratios. The ABCB1 3435C>T, 2677G>T/A, and 1236C>T polymorphisms affected neither tolvaptan pharmacokinetics nor its metabolism. Plasma 4β-OHC/TC and 25-OHD concentration were not correlated with plasma tolvaptan concentration. In a stratified analysis based on CYP3A5 genotype, plasma 4β-OHC/TC had a negative correlation with plasma tolvaptan concentration in the patients with the CYP3A5*1 allele, while the plasma concentration of 25-OHD did not. The CYP3A5*3/*3 genotype was associated with a higher serum sodium level in the patients with volume overload. The plasma concentration of 25-OHD had a positive correlation with the serum total bilirubin level. In conclusion, CYP3A5*3 but not ABCB1 genotypes elevated tolvaptan plasma exposure in heart failure patients. CYP3A5-deficient patients treated with tolvaptan had a higher serum sodium level. The CYP3A5 genotype altered the relationship between plasma tolvaptan and 4β-OHC. |
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1742-7835 |
| EISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1742-7843 |
| PubMed番号 |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
31652395 |
| 出版社DOI |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1111/bcpt.13355 |
| 著者版フラグ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
BCPT-126-353.pdf (846.9 kB)
