title: CYP3A activity based on plasma 4β-hydroxycholesterol during the early postpartum period has an effect on the plasma disposition of amlodipine.
abstract: 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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: naitou@hama-med.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kubono
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Biological Research Department, Sawai Pharmaceutical Co., Ltd., Osaka, Osaka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Deguchi
authors.affiliation: Biological Research Department, Sawai Pharmaceutical Co., Ltd., Osaka, Osaka, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Sugihara
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kanayama
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D049590:Postpartum Period / Q000097:blood*; D011247:Pregnancy; D013379:Substrate Specificity; D015854:Up-Regulation
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D002121:Calcium Channel Blockers; D006888:Hydroxycholesterols; C099828:cholest-5-ene-3,4-diol; D017311:Amlodipine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: 4β-hydroxycholesterol; Amlodipine; CYP3A; Pharmacokinetics; Pregnancy; Pregnancy-induced hypertension