title: Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro.
abstract: OBJECTIVE
  To investigate the transfer of therapeutically important fluoroquinolones: ciprofloxacin, ofloxacin and levofloxacin, through the isolated perfused human placenta, from the maternal to the fetal compartment.
  
  
  METHODS
  Isolated placental cotyledons from normal human term placentae were dually perfused with M199 medium enriched with 3g/l bovine serum albumin and 1g/l glucose. Perfusion rates were 12 and 6 ml/min in the maternal and fetal circulation, respectively. Maternal and fetal closed circulation was used to evaluate steady-state concentrations and transplacental gradient formation. Eighteen placentae were used in our study: six for each experiment with ciprofloxacin, ofloxacin and levofloxacin were added to the maternal circulation. Samples were collected from the maternal and fetal compartments. Antipyrine was used as a reference drug that crosses the placenta by simple diffusion. The concentrations of ciprofloxacin, ofloxacin, levofloxacin and antipyrine were measured by specific HPLC (high performance liquid chromatography) methods. Results are presented as mean+/-S.D.
  
  
  RESULTS
  In all the placentae, ciprofloxacin, ofloxacin, levofloxacin crossed the placenta from the maternal to the fetal compartment. The mean transplacental transfer percent of ciprofloxacin was 3.2+/-0.7% and the transplacental transfer index, the ratio of transplacental transfer between ciprofloxacin and antipyrine was 0.34+/-0.12. The mean transplacental transfer percent of ofloxacin was 3.7+/-2.4% and the transplacental transfer index was 0.33+/-0.3. The mean transplacental transfer percent of levofloxacin was 3.9+/-1.5% and the transplacental transfer index was 0.34+/-0.2.
  
  
  CONCLUSIONS
  Only a small fraction of ciprofloxacin, ofloxacin and levofloxacin passed from the maternal to the fetal compartment. This fraction is significantly smaller compared to antipyrine. This may indicate that there is a barrier to the transport of fluoroquinolones in human placenta.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Health, Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Hana
authors.initials: H
authors.lastname: Polachek
authors.forename: Gershon
authors.initials: G
authors.lastname: Holcberg
authors.forename: Gadi
authors.initials: G
authors.lastname: Sapir
authors.forename: Marina
authors.initials: M
authors.lastname: Tsadkin-Tamir
authors.forename: Joseph
authors.initials: J
authors.lastname: Polachek
authors.forename: Miriam
authors.initials: M
authors.lastname: Katz
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ben-Zvi
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005333:Fetus / Q000378:metabolism*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D064704:Levofloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin