Ratio of [3H]digoxin fetal concentration to maternal plasma concentration. Heterozygous mice were mated, and [3H]digoxin (0.05 mg/kg) was administered intravenously to pregnant dams at gestation day 15. At 4 hours or 24 hours after dosing, dams were euthanized, and fetuses from 3 litters were collected. Maternal plasma and fetal drug content and genotypes were determined as described in Methods. Open bars indicate wild-type values, hatched bars heterozygous values, and black bars Mdr1a–/–/1b–/– values. Values are expressed as mean [3H]digoxin concentration in fetal tissues (ng/g) normalized to maternal plasma [3H]digoxin concentration (ng/mL). Six to 16 fetuses of each genotype were analyzed. Average maternal plasma concentrations were 19.2 ± 1.6 ng/mL and 1.1 ± 0.15 ng/mL at 4 and 24 hours after digoxin administration, respectively. Error bars indicate SD. AP < 0.0001, BP < 0.005, vs. wild-type fetuses in pairwise comparison.