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高血压早产后和非产褥期女性内源性 CYP3A 标志物与氨氯地平血浆暴露和代谢的关系。

Relationships between endogenous CYP3A markers and plasma amlodipine exposure and metabolism in early postpartum and non-peripartum women with hypertension.

机构信息

Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

Pregnancy Hypertens. 2019 Jul;17:209-215. doi: 10.1016/j.preghy.2019.07.002. Epub 2019 Jul 4.

Abstract

OBJECTIVE

This study aimed to evaluate the relationship between endogenous CYP3A markers and plasma amlodipine (AML) exposure and metabolism parameters in early postpartum and non-peripartum women.

METHODS

Twenty-four AML-treated early postpartum women with hypertensive disorders of pregnancy and 30 non-peripartum women with essential hypertension were enrolled. Blood samples for determination of CYP3A markers including total cholesterol-adjusted 4β-hydroxycholesterol (4β-OHC/TC), 25-hydroxyvitamin D (25-OHD), and AML and its metabolites in plasma were collected at 24 h after the AML treatment.

RESULTS

The plasma 4β-OHC/TC in postpartum women was higher than that in non-peripartum women, while the plasma 25-OHD was lower. The postpartum women had a lower plasma AML concentration and its metabolic ratio was higher. The plasma 4β-OHC/TC decreased as the number of days post-delivery increased. The plasma AML concentration increased as the number of days post-delivery increased, while the metabolic ratio of AML declined slightly. Tendency toward negative correlations between the plasma 4β-OHC/TC but not 25-OHD, and AML concentration were observed in both postpartum and non-peripartum women. In both groups, the plasma 4β-OHC/TC was correlated with the metabolic ratio of AML.

CONCLUSIONS

The early postpartum women had higher plasma 4β-OHC and AML metabolism. The plasma 4β-OHC had positive relationships with amlodipine metabolism in both women groups. AML metabolism and plasma 4β-OHC may be useful as CYP3A markers in early postpartum and non-peripartum women.

摘要

目的

本研究旨在评估内源性 CYP3A 标志物与产后早期和非产褥期女性血浆氨氯地平(AML)暴露和代谢参数之间的关系。

方法

纳入 24 例患有妊娠高血压疾病的 AML 治疗产后早期妇女和 30 例患有原发性高血压的非产褥期妇女。在 AML 治疗后 24 小时采集血样,用于测定 CYP3A 标志物,包括总胆固醇校正的 4β-羟胆固醇(4β-OHC/TC)、25-羟维生素 D(25-OHD)和血浆中的 AML 及其代谢物。

结果

产后妇女的血浆 4β-OHC/TC 高于非产褥期妇女,而血浆 25-OHD 较低。产后妇女的血浆 AML 浓度较低,其代谢比值较高。随着产后天数的增加,血浆 4β-OHC/TC 降低。随着产后天数的增加,血浆 AML 浓度增加,而 AML 的代谢比值略有下降。产后和非产褥期妇女的血浆 4β-OHC/TC 与 AML 浓度呈负相关趋势,但 25-OHD 则无此趋势。在两组中,血浆 4β-OHC/TC 与 AML 的代谢比值相关。

结论

产后早期妇女的血浆 4β-OHC 和 AML 代谢较高。血浆 4β-OHC 与两组女性的 AML 代谢呈正相关。AML 代谢和血浆 4β-OHC 可能是产后早期和非产褥期妇女 CYP3A 标志物的有用指标。

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