title: Effect of albumin on transplacental transfer and distribution of rosiglitazone and glyburide.
abstract: OBJECTIVE
  The aims of this investigation were (i) to determine the rate and extent of rosiglitazone transfer across term human placenta, and (ii) to determine the effect of human serum albumin (HSA) on rosiglitazone and glyburide transfer and distribution.
  
  
  METHODS
  These aims were achieved by utilizing the technique of dual perfusion of placental lobule (DPPL). Each hypoglycemic drug was coperfused with the marker compound antipyrine (AP). In each experiment, the [3H]-isotope of the hypoglycemic drug and the [14C]-isotope of AP were added to enhance the detection limits of each drug. Human serum albumin (HSA) was added to both the maternal and fetal circuits in the experiments in which it was investigated.
  
  
  RESULTS
  Transplacental transfer of rosiglitazone and glyburide from the maternal to fetal circuits in media devoid of HSA was similar. However, the addition of HSA to the maternal and fetal circuits had different effects on the transfer and distribution of the two drugs, though their binding to HSA (99.8%) was almost identical. HSA increased the maternal (M) to fetal (F) transfer of rosiglitazone, as revealed by an increase in its F/M concentration ratio from 0.17 +/- 0.01 (in the absence of albumin) to 0.33 +/- 0.07 (p < 0.001). Moreover, the addition of albumin decreased the amount of rosiglitazone retained by placental tissue from 539 +/- 148 to 60 +/- 8 ng/g (p < 0.001). Conversely, the addition of HSA to the perfusion media resulted in a decrease in glyburide transfer, as revealed by the change of its F/M concentration ratio from 0.09 +/- 0.02 (in the absence of albumin) to 0.03 +/- 0.01 (p < 0.01). However, similar to rosiglitazone, glyburide retention by the tissue decreased from 103 +/- 26 to 19 +/- 6 ng/g (p < 0.001).
  
  
  CONCLUSIONS
  These data indicate that the binding of the two drugs to albumin, though similar, is only one of the factors that could affect their placental transfer and distribution.
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0587, USA.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Nanovskaya
authors.forename: Svetlana
authors.initials: S
authors.lastname: Patrikeeva
authors.forename: Sarah
authors.initials: S
authors.lastname: Hemauer
authors.forename: Valentina
authors.initials: V
authors.lastname: Fokina
authors.forename: Donald
authors.initials: D
authors.lastname: Mattison
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hankins
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Ahmed
mesh_terms: D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005905:Glyburide / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy; D000077154:Rosiglitazone; D012709:Serum Albumin / Q000378:metabolism; D045162:Thiazolidinediones / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D012709:Serum Albumin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005905:Glyburide