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CYP3A activity based on plasma 4ß-hydroxycholesterol during the early postpartum period has an effect on the plasma disposition of amlodipine.
Naito, Takafumi; Kubono, Naoko; Ishida, Takuya; Deguchi, Shuhei; Sugihara, Masahisa; Itoh, Hiroaki; Kanayama, Naohiro; Kawakami, Junichi.
Afiliación
  • Naito T; 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.
  • Kubono N; Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
  • Ishida T; Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
  • Deguchi S; Biological Research Department, Sawai Pharmaceutical Co., Ltd., Osaka, Osaka, Japan.
  • Sugihara M; Biological Research Department, Sawai Pharmaceutical Co., Ltd., Osaka, Osaka, Japan.
  • Itoh H; Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
  • Kanayama N; Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
  • Kawakami J; Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Drug Metab Pharmacokinet ; 30(6): 419-24, 2015 Dec.
Article en En | MEDLINE | ID: mdl-26654672
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bloqueadores de los Canales de Calcio / Amlodipino / Hipertensión Inducida en el Embarazo / Periodo Posparto / Citocromo P-450 CYP3A / Hidroxicolesteroles / Antihipertensivos Tipo de estudio: Diagnostic_studies / Observational_studies Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bloqueadores de los Canales de Calcio / Amlodipino / Hipertensión Inducida en el Embarazo / Periodo Posparto / Citocromo P-450 CYP3A / Hidroxicolesteroles / Antihipertensivos Tipo de estudio: Diagnostic_studies / Observational_studies Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido