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

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 4ß-hydroxycholesterol (4ß-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 4ß-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 4ß-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 4ß-OHC/TC but not 25-OHD, and AML concentration were observed in both postpartum and non-peripartum women. In both groups, the plasma 4ß-OHC/TC was correlated with the metabolic ratio of AML. CONCLUSIONS: The early postpartum women had higher plasma 4ß-OHC and AML metabolism. The plasma 4ß-OHC had positive relationships with amlodipine metabolism in both women groups. AML metabolism and plasma 4ß-OHC may be useful as CYP3A markers in early postpartum and non-peripartum women.

Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its relationship with their maternal background and neonatal health.

Few clinical studies have determined the quantitative transfer of vaginal chloramphenicol to circulating blood in pregnant women. This study aimed to evaluate the plasma concentration of chloramphenicol in pregnant women treated with trans-vaginal tablets and its relationship with maternal background and neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal chloramphenicol once daily for bacterial vaginosis and its suspected case were enrolled. The plasma concentration of chloramphenicol was determined using liquid chromatography coupled to tandem mass spectrometry at day 2 or later after starting the medication. The correlations between the maternal plasma concentration of chloramphenicol and the background and neonatal health at birth were investigated. Chloramphenicol was detected from all maternal plasma specimens and its concentration ranged from 0.043 to 73.1 ng/mL. The plasma concentration of chloramphenicol declined significantly with the administration period. The plasma concentration of chloramphenicol was lower at the second than the first blood sampling. No correlations were observed between the maternal plasma concentration of chloramphenicol and background such as number of previous births, gestational age at dosing, and clinical laboratory data. Neonatal infant health parameters such as birth-weight, Apgar score at birth, and gestational age at the time of childbearing were not related to the maternal plasma concentration of chloramphenicol. Vaginal chloramphenicol transfers to circulating blood in pregnant women. The maternal plasma concentration of chloramphenicol varied markedly and was associated with the administration day, but not with maternal background or her neonatal health.

CYP3A activity based on plasma 4ß-hydroxycholesterol during the early postpartum period has an effect on the plasma disposition of amlodipine.

This study aimed to evaluate plasma 4ß-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 4ß-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 4ß-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 4ß-hydroxycholesterol between the postpartum periods. The plasma concentration of 4ß-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 4ß-hydroxycholesterol. In conclusion, early postpartum women possessed higher CYP3A activity based on plasma 4ß-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.

Amlodipine passage into breast milk in lactating women with pregnancy-induced hypertension and its estimation of infant risk for breastfeeding.

BACKGROUND: Few clinical reports have been published on amlodipine passage into breast milk in lactating women. OBJECTIVES: The aims of this study were to evaluate the plasma concentration of amlodipine and its passage into breast milk in lactating women with pregnancy-induced hypertension and to estimate the risk for breastfeeding infants. METHODS: Thirty-one lactating women receiving oral amlodipine once daily for pregnancy-induced hypertension were enrolled. Pre-dose plasma and milk concentrations of amlodipine were determined at day 6 or later after starting the medication. Relative infant dose (RID) as an infant risk for breastfeeding was calculated by dividing the infant dose via milk by the maternal dose. RESULTS: The mean maternal dose of amlodipine was 6.0 mg. The medians of the plasma and milk concentrations of amlodipine were 15.5 and 11.5 ng/mL, respectively. Interindividual variation was observed in the amlodipine dose and body weight-adjusted milk concentrations (interquartile range [IQR], 96.7-205 ng/mL per mg/kg). The median and IQR of the amlodipine concentration ratio of milk to plasma were 0.85 and 0.74 to 1.08, respectively. The medians of infant birth weight and daily amlodipine dose via milk were 2170 g and 4.2 µg/kg, respectively. The median of the RID of amlodipine was 4.2% (IQR, 3.1%-7.3%). CONCLUSION: Lactating women with pregnancy-induced hypertension had higher plasma concentrations of amlodipine during the early postpartum period. Oral amlodipine transferred into breast milk at the same level as that of plasma. However, the RID of amlodipine in most patients was less than 10%.