title: Insulin glargine safety in pregnancy: a transplacental transfer study.
abstract: OBJECTIVE
  Insulin glargine (Lantus) is an extended-action insulin analog with greater stability and duration of action than regular human insulin. The long duration of action and decreased incidence of hypoglycemia provide potential advantages for its use in pregnancy. However, the placental pharmacokinetics of insulin glargine have not been studied. Therefore, the objective of this study was to determine whether insulin glargine crosses the human placenta using the human perfused placental lobule technique.
  
  
  METHODS
  Placentae were obtained with informed consent after elective cesarean section delivery of noncomplicated term pregnancies. Insulin glargine, at a therapeutic concentration of 150 pmol/l (20 microU/ml) was added to the maternal circulation. Additional experiments were carried out at insulin glargine concentrations 1,000-fold higher than therapeutic levels (150, 225, and 300 nmol/l). A subsequent perfusion for which the maternal circuit remained open and insulin glargine was continuously infused at 150 pmol/l was completed for further confirmation of findings. The appearance of insulin glargine in the fetal circulation was analyzed by a chemiluminescence immunoassay.
  
  
  RESULTS
  Results from perfusions carried out at therapeutic concentrations (150 pmol/l) of insulin glargine showed no detectable insulin glargine in the fetal circuit. After perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/l, the rate of transfer remained low at 0.079 +/- 0.01, 0.14, and 0.064 pmol . min(-1) . g tissue(-1), respectively.
  
  
  CONCLUSIONS
  Insulin glargine, when used at therapeutic concentrations, is not likely to cross the placenta.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, the Hospital for Sick Children, Toronto, Ontario, Canada. gkoren@sickkids.ca
authors.forename: Erika K
authors.initials: EK
authors.lastname: Pollex
authors.forename: Denice S
authors.initials: DS
authors.lastname: Feig
authors.forename: Angelika
authors.initials: A
authors.lastname: Lubetsky
authors.forename: Paul M
authors.initials: PM
authors.lastname: Yip
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D001692:Biological Transport; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine