The placental transfer of sufentanil: effects of fetal pH, protein binding, and sufentanil concentration.
This study investigated factors that influence the placental transfer of sufentanil using the dual-perfused, single-cotyledon human placental model. Placentas were collected from healthy women. Experiments were designed to elucidate the effects of maternal protein binding, changing maternal sufentanil concentration (1, 10, 20, and 100 ng/mL) and decreasing fetal pH (fetal acidemia 7.2, 7.0, 6.8) on the placental transfer of sufentanil. Sufentanil crossed the placenta rapidly at a rate two-thirds that of the transfer marker, antipyrine. Sufentanil transfer increased linearly with the maternal concentration (r = 0.999). Sufentanil/antipyrine maternal to fetal (M-->F) transfer ratios were significantly reduced (0.66 +/- 0.05 vs 0.40 +/- 0.04, P < 0.05) when fresh frozen plasma was added to the maternal circuit to enhance protein binding. Fetal pH and sufentanil transfer were related because sufentanil M-->F clearance increased significantly as the fetal pH decreased (r = 0.973, P < 0.05). Sufentanil appears to cross the placenta by passive diffusion but is modulated by the degree of maternal protein binding. Sufentanil M-->F transfer is enhanced by fetal acidemia.
Johnson
R F
RF
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2125, USA. ray.johnson@mcmail.vanderbilt.edu-e-mail
Herman
N
N
Arney
T L
TL
Johnson
H V
HV
Paschall
R L
RL
Downing
J W
JW
D000328:Adult; D000701:Analgesics, Opioid / Q000378:metabolism / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D017409:Sufentanil / Q000378:metabolism / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D001798:Blood Proteins; D017409:Sufentanil