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

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.

Keywords: 25-Hydroxyvitamin D; 4β-Hydroxycholesterol; Amlodipine; CYP3A; Hypertensive disorders of pregnancy; Metabolism.

Publication types

  • Observational Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Amlodipine / administration & dosage
  • Amlodipine / therapeutic use*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Biomarkers / blood
  • Case-Control Studies
  • Cytochrome P-450 CYP3A / blood*
  • Female
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Middle Aged
  • Peripartum Period
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / drug therapy*
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / blood
  • Pregnancy Complications, Cardiovascular / drug therapy*
  • Prenatal Care
  • Young Adult

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Amlodipine
  • Cytochrome P-450 CYP3A