Effect of albumin on transplacental transfer and distribution of rosiglitazone and glyburide.
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.
Nanovskaya
Tatiana N
TN
Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0587, USA.
Patrikeeva
Svetlana
S
Hemauer
Sarah
S
Fokina
Valentina
V
Mattison
Donald
D
Hankins
Gary D
GD
Ahmed
Mahmoud S
MS
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*
D007004:Hypoglycemic Agents; D012709:Serum Albumin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005905:Glyburide