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CYP3A activity based on plasma 4β-hydroxycholesterol during the early postpartum period has an effect on the plasma

Takafumi Naito1, Naoko Kubono1, Takuya Ishida1

  • 1Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.

Drug Metabolism and Pharmacokinetics
|December 15, 2015
PubMed

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.

Keywords:
4β-hydroxycholesterolAmlodipineCYP3APharmacokineticsPregnancyPregnancy-induced hypertension

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