Biomaterial Database

Sufentanil transfer in the human placenta during in vitro perfusion. 1997

B R Krishna, and M I Zakowski, and G J Grant

Department of Anesthesiology, New York University Medical Center, NY 10016, USA.

OBJECTIVE Sufentanil, a lipophilic opioid, is used to provide analgesia for labour and Caesarean section, but may cause neonatal depression. Factors affecting placental transfer of sufentanil were investigated using human placentas. METHODS Transfer and uptake of sufentanil by the human placenta were studied using a single pass (open) in vitro perfusion model. The effects of change in sufentanil concentration (1-100 ng.ml-1) and change in fetal pH (range 7.4-6.8) on placental transfer were studied. Placental metabolism of sufentanil and the effects of maternal protein content (fresh human plasma, albumin 4%, Media 199) on placental transfer were also investigated utilizing a closed (recirculated) in vitro perfusion system. RESULTS Sufentanil transfer was 2% at five minutes and plateaued at 12% by 45 min. The clearance index (CI = sufentanil clearance/antipyrine clearance) was 0.56 +/- 0.2 for maternal to fetal (MTF) and 0.44 +/- 0.2 in the fetal to maternal (FTM) directions (P = NS). The CI was 0.5 +/- 0.2 for 1 ng.ml-1 and 0.61 +/- 0.3 for 100 ng.ml-1 sufentanil concentration (P = N.S.). The placenta contained 7.1 +/- 2 and 9.8 +/- 3 ng.g-1 sufentanil following MTF and FTM perfusions for 90 min at 1 ng.ml-1. The placenta did not metabolize sufentanil. After one hour MTF washout, placental sufentanil content was 2.3 +/- .5 ng.g-1 with 0.08 ng.ml-1 sufentanil in the umbilical vein. Maternal plasma decreased MTF CI from 0.41 +/- 0.1 for albumin and 0.4 +/- 0.1 for Media 199 to 0.17 +/- .06 for plasma (P < 0.05). Decreasing fetal pH increased MTF CI from 0.57 +/- .13 at pH 7.4 to 1.6 +/- .4 at pH 6.8 (P < 0.05). CONCLUSIONS Sufentanil crossed the placenta by passive diffusion and accumulated in placental tissue, which acted as a drug depot, slowing the initial transfer. Placental transfer was decreased by maternal plasma proteins, but not by albumin. Fetal acidosis increased placental transfer. Due to its low initial umbilical vein concentration, sufentanil may be the opioid of choice when delivery is imminent (< 45 min).

UI	MeSH Term	Description	Entries
D007231	Infant, Newborn	An infant during the first 28 days after birth.	Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007743	Labor, Obstetric	The repetitive uterine contraction during childbirth which is associated with the progressive dilation of the uterine cervix (CERVIX UTERI). Successful labor results in the expulsion of the FETUS and PLACENTA. Obstetric labor can be spontaneous or induced (LABOR, INDUCED).	Obstetric Labor
D008431	Maternal-Fetal Exchange	Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission.	Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D010920	Placenta	A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).	Placentoma, Normal,Placentome,Placentas,Placentomes
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D002585	Cesarean Section	Extraction of the FETUS by means of abdominal HYSTEROTOMY.	Abdominal Delivery,Delivery, Abdominal,C-Section (OB),Caesarean Section,Postcesarean Section,Abdominal Deliveries,C Section (OB),C-Sections (OB),Caesarean Sections,Cesarean Sections,Deliveries, Abdominal
D004058	Diffusion	The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT.	Diffusions