TRANSFER OF COCAINE BY THE PERFUSED HUMAN PLACENTA - THE EFFECT OF BINDING TO SERUM-PROTEINS

OBJECTIVES: Our purpose was to investigate the transfer of cocaine acr oss human placenta and to measure the binding of cocaine to maternal a nd cord sera and to assess the effect of binding on transfer. STUDY DE SIGN: Cocaine transfer by the in vitro perfused human placenta was stu died under controlled experimental conditions. Protein binding of coca ine was measured by ultrafiltration in 10 pairs of maternal and cord s era and was compared with 12 sera from nonpregnant females. RESULT: Wi th perfusates of albumin (5 gm/dl) in buffer cocaine clearance was 1.0 8 t 0.52 ml/min, threefold greater than that of the water-soluble mark er L-glucose. Transfer was bidirectional and nonsaturable over a conce ntration of 0.02 to 4000 ng/ml. Cocaine was not detectably metabolized during perfusion. Replacement of albumin-buffer with human serum as m aternal perfusate reduced the transfer rate by almost 50%, p < 0.02. B inding of cocaine was greatest by serum from the nonpregnant female > pregnant female (not significant) > cord serum (p < 0.02) = albumin bu ffer. CONCLUSIONS: Cocaine is rapidly transferred across the placenta by simple diffusion without metabolic conversion. Transfer, although d iminished, remains rapid in spite of binding to serum proteins. These several factors plus the poor binding by cord serum conspire to increa se fetal exposure to the drug.