Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer.
OBJECTIVE
This study compares the human placental transport of glyburide, glipizide, chlorpropamide, and tolbutamide.


METHODS
The recirculating single cotyledon human placenta model tested maternal-to-fetal transport in term placentas perfused immediately after delivery. Drug levels were measured by high-performance liquid chromatography and liquid scintillation spectrometry, and transport rates were calculated by comparing maternal and fetal concentrations.


RESULTS
The transport of these substances differed significantly over a tenfold range (analysis of variance, p < 0.0008). A significant association exists by multiple linear regression between drug transfer and molecular weight, dissociation constant, and the octanol-water partition coefficient (R2 = 0.91, p < 0.0001).


CONCLUSIONS
There is significant variability in human placental transfer rates of the oral hypoglycemics, which strongly correlates with molecular properties. These data suggest that less fetal exposure may occur with second-generation sulfonylureas and anticipate that regression models may be useful in selecting agents that minimize placental transport to the fetus.
Elliott
B D
BD
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio 78284-7836.
Schenker
S
S
Langer
O
O
Johnson
R
R
Prihoda
T
T
D000284:Administration, Oral; D000704:Analysis of Variance; D000983:Antipyrine / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D002747:Chlorpropamide / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005913:Glipizide / Q000493:pharmacokinetics; D005905:Glyburide / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D008970:Molecular Weight; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012044:Regression Analysis; D014044:Tolbutamide / Q000493:pharmacokinetics
D007004:Hypoglycemic Agents; D014044:Tolbutamide; D005905:Glyburide; D000983:Antipyrine; D002747:Chlorpropamide; D005913:Glipizide