title: Transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate using the ex vivo human placenta perfusion model in Chinese Hans population.
abstract: OBJECTIVE
  The objective of the study was to determine transplacental of oseltamivir phosphate (OP) and its active metabolite oseltamivir carboxylate (OC) using the ex vivo human placental perfusion model in Chinese Hans population.
  
  
  METHODS
  Perfusion studies were performed on 20 placentas from healthy term pregnancies. Concentrations typical for 75 mg, twice-daily oral dose were tested (OP 65.2 ng/ml and OC 348 ng/ml), along with the positive control antipyrine 0.1 mg/ml. Each perfusion experiment was conducted for 180 min while samples were taken from both maternal and fetal compartments. Concentrations of OP and its metabolite OC were determined by ultrafast-performance liquid chromatography/tandem mass spectrometry. Integrity and viability of the placenta were determined by measuring fetal volume loss, pH, pO2, ΔhCG, glucose consumption and lactate production during the perfusion experiments.
  
  
  RESULTS
  Following 3 h of perfusion, the fetal transfer rates of OP and its metabolite OC were 12.39%±3.26%, 10.17%±2.03%, respectively. The clearance indexes of OP and OC were 0.36 ± 0.11 and 0.29 ± 0.06, respectively.
  
  
  CONCLUSIONS
  These data suggest that OP and its metabolite OC pass through the healthy term placenta at a small amount according to the ex vivo human placental perfusion model, fetal exposure must be considered when treating pregnant women with OP.
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: c Department of Pediatrics , First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Duan
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yao
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: b Obstetrics and Gynecology.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Tian
authors.affiliation: a Department of Clinical Pharmacy.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000998:Antiviral Agents / Q000032:analysis / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007251:Influenza, Human / Q000628:therapy; D008431:Maternal-Fetal Exchange; D053139:Oseltamivir / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics*; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: Ex vivo human placenta perfusion model; influenza; oseltamivir phosphate; pregnancy; transplacental transfer