The placental transfer of propofol was investigated using the in vitro dually perfused cotyledon model of the human placenta, and the effects of protein binding in the foetal perfusate were examined. Both maternal and foetal circulations were perfused in a single-pass mode and > 30 min of stabilization was allowed before adding propofol and antipyrine to the maternal perfusate. The placental clearances of propofol were significantly increased by the augmented albumin concentrations in the foetal perfusate (1.68 (SD 0.68), 3.08 (1.55), 4.79 (1.76), 5.75 (1.89) and 7.03 (1.46) ml h-1 g-1 at the albumin concentrations of 4.4, 11, 22, 33 and 44 g litre-1, respectively). Although the total propofol concentration in the foetal vein increased significantly with increasing albumin concentration, the concentration of free propofol remained unchanged. These results indicate that binding to foetal albumin is a determining feature in the control of the placental transfer of propofol, and that the pharmacological effects of propofol on the foetus can be expected to be fairly constant and predictable from the maternal propofol concentration.
Uterine and umbilical blood flows are determinant features in controlling the placental transfer of propofol, and, therefore, changes in these variables would significantly affect the extent of fetal exposure to propofol.
The findings suggest that the reduction of propofol injection pain by FA may be explained, at least in part, by a reduction in the free propofol concentration.
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