GLYBURIDE CROSSES THE PLACENTA IN-VIVO IN PREGNANT RATS

Non-insulin-dependent diabetes mellitus (NIDDM) is normally treated by oral hypoglycaemic agents, but their use is excluded during pregnancy because of their potential teratogenic and hypoglycaemic effects on t he fetus. This caveat was recently questioned as glyburide was shown t o cross an isolated cotyledon in vitro in insignificant amounts. In th e present study, placental transport of glyburide in vivo was examined as an indispensable step towards clinical trials. Tritiated glyburide , C-14 albumin or C-14-labelled diazepam were injected into 13, 9 and 11 pregnant rats, respectively and the radioactivity was measured ther eafter in maternal blood and in whole fetal extracts. The ratios betwe en radioactivity in fetal tissue to that in maternal blood for glyburi de (0.535 +/- 0.068) were similar to those of diazepam (O.641 +/- 0.05 7) which readily crosses the placenta. However, they differed signific antly from those for albumin (0.048 +/- 0.0004) which does not cross. Moreover, glyburide in fetal tissue consistently reflected its concent ration in maternal blood when measured at consecutive intervals after intravenous injection in the mother. In contrast, albumin in fetal tis sue was low at all time points regardless of its levels in maternal bl ood when measured at different times after injection. These data sugge st that glyburide crosses the placenta of pregnant rats and should the refore be considered with caution as a hypoglycaemic agent in the trea tment of gestational diabetes.