PLACENTAL-TRANSFER OF SULINDAC AND ITS ACTIVE SULFIDE METABOLITE IN HUMANS

OBJECTIVE: Our aim was to investigate whether the human placenta is permeable to sulindac or its active sulfide metabolite. STUDY DESIGN: Nine pregnant patients (median gestational age [range]: 31.8 [24.3 to 36.4] weeks) were given a 200 mg oral dose of sulindac 5.5 (4.4 to 6.7) hours before 18 intravascular transfusions for rhesus or Kell alloimmunization. At each procedure maternal and fetal serum levels of sulindac and the active sulfide metabolite were measured by high-performance liquid chromatography. RESULTS: The maternal sulfide level was significantly higher than the fetal sulfide levels, but no significant difference was noted between maternal and fetal sulindac levels. The sulfide fetal/maternal ratio was significantly lower than the sulindac fetal/maternal ratio. The sulfide/sulindac ratio was significantly higher in maternal serum versus fetal serum. The sulfide/sulindac ratio correlated with time from drug ingestion to sampling on the maternal side only. In patients studied on more than one occasion no consistent relationship between fetal sulindac, fetal sulfide, or fetal sulfide/sulindac ratio, and gestational age could be demonstrated. CONCLUSION: The placenta is permeable to sulindac but less so to its active sulfide metabolite. The reduction of sulindac to its active sulfide metabolite is decreased in the human fetus.