title: Transfer of methohexital across the perfused human placenta.
abstract: OBJECTIVE
  To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model.
  
  
  METHODS
  Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and fetal-to-maternal (F-->M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model.
  
  
  METHODS
  Obstetric anesthesia laboratories of two university medical centers.
  
  
  METHODS
  No patient participation occurred as placentae were obtained after delivery.
  
  
  METHODS
  M-->F and F-->M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL).
  
  
  RESULTS
  Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 +/- 0.11 for the M-->F perfusions was significantly greater (p < or = 0.05) than in the F-->M direction (0.61 +/- 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-->F 0.87 +/- 0.12 and F-->M 0.95 +/- 0.11).
  
  
  CONCLUSIONS
  Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.
authors.affiliation: Department of Anesthesiology, New York Presbyterian Hospital-Weill Medical College of Cornell University, NY 10021, USA. nlherman@med.cornell.edu
authors.forename: N L
authors.initials: NL
authors.lastname: Herman
authors.forename: A T
authors.initials: AT
authors.lastname: Li
authors.forename: T K
authors.initials: TK
authors.lastname: Van Decar
authors.forename: R F
authors.initials: RF
authors.lastname: Johnson
authors.forename: R W
authors.initials: RW
authors.lastname: Bjoraker
authors.forename: J W
authors.initials: JW
authors.lastname: Downing
authors.forename: D
authors.initials: D
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000983:Antipyrine / Q000493:pharmacokinetics; D002823:Chorion / Q000098:blood supply; D002824:Chorionic Villi; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005947:Glucose / Q000032:analysis; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D008431:Maternal-Fetal Exchange; D008723:Methohexital / Q000493:pharmacokinetics*; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D015203:Reproducibility of Results; D014022:Tissue Survival
chemical_list: D000418:Albumins; D018686:Anesthetics, Intravenous; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019344:Lactic Acid; D008723:Methohexital; D005947:Glucose; D000983:Antipyrine