Naito Takafumi, Kubono Naoko, Ishida Takuya, Deguchi Shuhei, Sugihara Masahisa, Itoh Hiroaki, Kanayama Naohiro, Kawakami Junichi
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Drug Metab Pharmacokinet. 2015 Dec;30(6):419-24. doi: 10.1016/j.dmpk.2015.08.008. Epub 2015 Sep 3.
This study aimed to evaluate plasma 4β-hydroxycholesterol as an endogenous marker of CYP3A4/5 activity in early postpartum women and its impact on the plasma disposition of amlodipine. Twenty-seven early postpartum women treated with amlodipine for pregnancy-induced hypertension were enrolled. The plasma concentration of 4β-hydroxycholesterol and its ratio to cholesterol in postpartum and in non-perinatal women were evaluated. The predose plasma concentration of amlodipine was determined at steady state. The medians of the plasma 4β-hydroxycholesterol concentration at day 0-3 and 8-21 after delivery were 146 and 161 ng/mL, respectively. No significant difference was observed in the plasma concentration of 4β-hydroxycholesterol between the postpartum periods. The plasma concentration of 4β-hydroxycholesterol and its ratio to cholesterol in postpartum women were significantly higher than those in non-perinatal women. A large individual variability was observed in the dose-normalized plasma concentration of amlodipine in early postpartum women. A weak negative correlation was observed between the dose-normalized plasma concentration of amlodipine and the plasma concentration of 4β-hydroxycholesterol. In conclusion, early postpartum women possessed higher CYP3A activity based on plasma 4β-hydroxycholesterol and had a large pharmacokinetic variability in amlodipine. CYP3A activity during the early postpartum period had an effect on the plasma disposition of amlodipine.
本研究旨在评估血浆4β-羟基胆固醇作为产后早期女性CYP3A4/5活性的内源性标志物及其对氨氯地平血浆处置的影响。纳入了27例因妊娠高血压接受氨氯地平治疗的产后早期女性。评估了产后女性和非围产期女性血浆中4β-羟基胆固醇的浓度及其与胆固醇的比值。在稳态下测定氨氯地平的给药前血浆浓度。分娩后0 - 3天和8 - 21天血浆4β-羟基胆固醇浓度的中位数分别为146和161 ng/mL。产后不同时期之间4β-羟基胆固醇的血浆浓度未观察到显著差异。产后女性血浆中4β-羟基胆固醇的浓度及其与胆固醇的比值显著高于非围产期女性。产后早期女性氨氯地平的剂量标准化血浆浓度存在较大的个体差异。氨氯地平的剂量标准化血浆浓度与4β-羟基胆固醇的血浆浓度之间观察到弱负相关。总之，基于血浆4β-羟基胆固醇，产后早期女性具有较高的CYP3A活性，且氨氯地平的药代动力学变异性较大。产后早期的CYP3A活性对氨氯地平的血浆处置有影响。
