The relationship between maternal and fetal plasma protein binding of methadone in the ewe during the third trimester

The binding of methadone to maternal and fetal plasma proteins was determined throughout the third trimester in the pregnant ewe. Blood was sampled from chronic indwelling catheters placed in the maternal aorta and fetal aorta. Methadone binding was determined by use of equilibrium dialysis with (³H)-methadone. Maternal binding ranged from 50.4 to 89.5%, with a mean of 76.2 ±1.3 (SE)%. Fetal binding was initially significantly lower than maternal binding, but increased rapidly in the last two weeks before parturition. Prior to 130 days gestation, the ratio of fetal binding to maternal binding was 0.40 ± 0.03. This binding ratio increased to 0.82 ± 0.08 in the last few days of pregnancy. Preliminary results suggested that maternal binding was higher in the early post-partum period. These results demonstrate that the relationship between maternal and fetal plasma binding of methadone changes rapidly towards the end of pregnancy, and fetal binding approaches maternal binding at parturition.