Reina Taguchi1, Takafumi Naito2, Naoko Kubono1, Noriyoshi Ogawa3, Hiroaki Itoh4, Junichi Kawakami1. 1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan. 2. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: naitou@hama-med.ac.jp. 3. Department of Rheumatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 4. Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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.
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.