Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Pregnancy Hypertens. 2019 Jul;17:209-215. doi: 10.1016/j.preghy.2019.07.002. Epub 2019 Jul 4.
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.
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.
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.
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.
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。
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。
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。
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。