Transfer of Cocaine by the Perfused Human Placenta: The Effect of Binding to Serum Proteins

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Abstract

OBJECTIVES

Our purpose was to investigate the transfer of cocaine across human placenta and to measure the binding of cocaine to maternal and cord sera and to assess the effect of binding on transfer.

STUDY DESIGN

Cocaine transfer by the in vitro perfused human placenta was studied under controlled experimental conditions. Protein binding of cocaine was measured by ultrafiltration in 10 pairs of maternal and cord sera and was compared with 12 sera from nonpregnant females.

RESULT

With perfusates of albumin (5 gm/dl) in buffer cocaine clearance was 1.08 +/-0.52 ml/min, threefold greater than that of the water-soluble marker L-glucose. Transfer was bidirectional and nonsaturable over a concentration of 0.02 to 4000 ng/ml. Cocaine was not detectably metabolized during perfusion. Replacement of albumin-buffer with human serum as maternal perfusate reduced the transfer rate by almost 50%, p < 0.02. Binding of cocaine was greatest by serum from the nonpregnant female > pregnant female (not significant) > cord serum (p < 0.02) = albumin buffer.

CONCLUSIONS

Cocaine is rapidly transferred across the placenta by simple diffusion without metabolic conversion. Transfer, although diminished, remains rapid in spite of binding to serum proteins. These several factors plus the poor binding by cord serum conspire to increase fetal exposure to the drug. (AM J OBSTET GYNECOL 1993;169:1418-23.)

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