Transfer of Glyburide and Glipizide Into Breast Milk

Abstract

Type 2 diabetes is becoming increasingly prevalent worldwide. In particular, the incidence has risen in younger persons despite a prevailing view that the elderly are especially at risk. Women in their reproductive yearsare part of this trend. Currently, insulin usually is administered before conception if a pregnancy is planned and continued into the postpartum period if the woman chooses to breast feed her infant. Many women, however, want to resume oral hypoglycemic drugs after giving birth. Furthermore, in much of the world, injectable insulin is prohibitively costly. Both glyburide and glipizide are easily administered and effective, but whether they are safe for nursing infants remains uncertain. The first of the present studies was planned to show whether these drugs are excreted into breast milk, and the second was a daily-dose study done to learn whether the infants of women taking the drugs become hypoglycemic. Eight women received a single oral dose of 5 or 10 mg glyburide, and drug concentrations were measured in both maternal blood and breast milk for 8 hours. The mean maximum theoretical infant dose (MTID), given as a percent of the weight-adjusted maternal dose (WAMD), was less than 1.5% for the 5-mg dose and less than 0.7% for the 10-mg dose. The mean WAMD values were 0.06 and 0.14 mg/kg, respectively. Glyburide was not detected in any of 29 samples of breast milk during the 8-hour study. The drug was, however, present in maternal plasma. In the daily-dose study, five women received 5 mg daily of either glyburide or glipizide starting on the first postpartum day. Drug levels in maternal blood and breast milk were estimated 5 to 16 days after delivery. Only one woman had detectable drug (glipizide) in her serum. The mean MTID as a percent of the WAMD was less than 28% for glyburide and less than 27% for glipizide. These high values were attributed to the insensitivity of the assay. Neither of the drugs was found in breast milk, and all three infants who were exclusively breast fed had normal blood glucose concentrations. Although more data are needed, these small-scale studies suggest that parturients with type 2 diabetes can take glyburide or glipizide in the doses tested even if they breast feed their infants.