title: Transplacental passage of vancomycin in the ex vivo human perfusion model.
abstract: OBJECTIVE
  To determine maternal-fetal transplacental passage of vancomycin in the ex vivo human placental perfusion model.
  
  
  METHODS
  Six term placentas were collected immediately after delivery and perfused with physiologic medium using the single cotyledon perfusion system. Vancomycin was added to the maternal medium and perfused through the maternal circulation of the cotyledon. Over a 1-h period in an open system, samples of the perfusate were collected at defined intervals from the fetal venous catheter and from the maternal effluence to assess vancomycin transfer. Thereafter, the system was closed for 1-5 h to establish accumulation. Transport fraction and clearance indexes were calculated by perfusing antipyrine 14C (positive control). Vancomycin was estimated by high pressure liquid chromatography and antipyrine 14C concentration was determined by liquid scintillation.
  
  
  RESULTS
  Mean vancomycin maternal peak and trough concentrations ranged from 30.0 to 51.5 microg/ml and 7.7 to 16.4 microg/ml, respectively. Clearance indexes were minimal with a mean peak range of 0.000-0.080 and a mean trough range of 0.00-0.17. For each placenta, transport fraction for antipyrine 14C was > 1.85 with a single pass of > 40%. No accumulation of vancomycin was noted when the system was closed for 1-5 h. The mean peak clearance index was zero after perfusing the placenta for up to 5 h with 35.8 microg/ml of vancomycin.
  
  
  CONCLUSIONS
  Transplacental passage of vancomycin was minimal in the ex vivo human placental perfusion model, with no detectable accumulation.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas, Dallas, TX, USA. Michael.Hnat@UTSouthwestern.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hnat
authors.forename: Julie
authors.initials: J
authors.lastname: Gainer
authors.forename: Roger E
authors.initials: RE
authors.lastname: Bawdon
authors.forename: George D
authors.initials: GD
authors.lastname: Wendel
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000493:pharmacokinetics*; D000983:Antipyrine / Q000378:metabolism; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000098:blood supply; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D011247:Pregnancy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014640:Vancomycin / Q000032:analysis / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D014640:Vancomycin; D000983:Antipyrine
references.citation: Am J Obstet Gynecol. 1989 Oct;161(4):977-81
references.pmid: 2801848
references.citation: Antimicrob Agents Chemother. 1998 Jun;42(6):1517-9
references.pmid: 9624508
references.citation: Am J Health Syst Pharm. 1997 Jan 15;54(2):181-4
references.pmid: 9117807
references.citation: Am J Hosp Pharm. 1993 Jul;50(7):1360, 1362-3
references.pmid: 8362868
references.citation: Obstet Gynecol. 1991 Nov;78(5 Pt 2):908-11
references.pmid: 1923224
references.citation: Clin Infect Dis. 2000 Jul;31(1):76-9
references.pmid: 10913400
references.citation: Am J Obstet Gynecol. 2000 Oct;183(4):859-62
references.pmid: 11035326
references.citation: N Engl J Med. 2001 Sep 13;345(11):804-9
references.pmid: 11556301
references.citation: Contrib Gynecol Obstet. 1985;13:32-9
references.pmid: 3888528