title: Placental transfer and mammary excretion of a novel angiotensin receptor blocker fimasartan in rats.
abstract: Fimasartan (FMS) is a potent angiotensin receptor blocker for the treatment of mild to moderate hypertension. This study aimed to evaluate the transfer of FMS to fetus and breast milk in rats.
  
  
  
  In order to study the transfer to the fetus and nursing pup, pregnant and nursing maternal rats were administered with FMS by a constant intravenous infusion to reach target plasma concentrations of 200 ng/mL and 100 ng/mL. The concentrations of FMS in plasma, placenta, amniotic fluid, fetus, and milk were determined by a validated LC-MS/MS assay.
  
  
  
  Upon constant intravenous infusion, the plasma FMS concentration reached the target steady state concentrations (Css = 200 ng/mL and 100 ng/mL) in 24 h. The tissue-to-plasma partition coefficients (Kp) for placenta, amniotic fluid, and milk were obtained based on the observed FMS concentrations in the tissues and Css. The Kp values for all tissues were not different between high (Css = 200 ng/mL) and low (Css = 100 ng/mL) dose groups. While the mean Kp of the placenta was 44.6-59.0 %, the mean Kp was 1.3-1.7 % for the amniotic fluid and 14.9-17.0 % for fetus. The mean Kp of milk was 10.4-15.2 %.
  
  
  
  Placental transfer and milk excretion of FMS was relatively lower compared to other angiotensin receptor blockers.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, South Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Shin
authors.affiliation: Boryung Pharm. Co., Ltd., Seoul, South Korea.
authors.forename: Yong-Ha
authors.initials: YH
authors.lastname: Chi
authors.affiliation: College of Pharmacy, Sunchon National University, Sunchon, Jeonnam, South Korea.
authors.forename: Soo-Heui
authors.initials: SH
authors.lastname: Paik
authors.affiliation: Boryung Pharm. Co., Ltd., Seoul, South Korea.
authors.forename: Joo-Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.affiliation: College of Pharmacy, University of Florida, Orlando, FL, USA.
authors.forename: Jürgen B
authors.initials: JB
authors.lastname: Bulitta
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup Gyeongsan-si, Gyeongbuk, 712-702, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Joo
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup Gyeongsan-si, Gyeongbuk, 712-702, South Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup Gyeongsan-si, Gyeongbuk, 712-702, South Korea.
authors.forename: Kwon-Yeon
authors.initials: KY
authors.lastname: Weon
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup Gyeongsan-si, Gyeongbuk, 712-702, South Korea. bsshin@cu.ac.kr.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D007262:Infusions, Intravenous; D007774:Lactation / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000008:administration & dosage / Q000097:blood*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D011743:Pyrimidines; D013777:Tetrazoles; C558933:fimasartan
keywords: Angiotensin receptor blocker; Fimasartan; Hypertension; Maternal-fetal transfer; Milk secretion