title: Maternal-fetal transport kinetics of carboplatin in the perfused human placental lobule: in vitro study.
abstract: OBJECTIVE
  Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal-fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro.
  
  
  METHODS
  Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters.
  
  
  RESULTS
  The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 +/- 0.10, 1.06 +/- 0.06, 1.00 +/- 0.02, 0.98 +/- 0.01, and 0.99 +/- 0.01, respectively, times the antipyrine reference value. Student's t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.60 +/- 2.01% of injected bolus dose, representing 13.1% of reference marker value. Student's t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences.
  
  
  CONCLUSIONS
  We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.
authors: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Kuwait, Kuwait. rania@hsc.edu.kw
authors: Eyad
authors: E
authors: Al-Saleh
authors: Moorkath
authors: M
authors: Nandakumaran
authors: Ibrahim
authors: I
authors: Al-Rashdan
authors: Jehad
authors: J
authors: Al-Harmi
authors: Majed
authors: M
authors: Al-Shammari
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D000983:Antipyrine / Q000493:pharmacokinetics; D001682:Biological Availability; D016190:Carboplatin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology; D008657:Metabolic Clearance Rate; D010477:Perfusion; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016190:Carboplatin; D000983:Antipyrine