Placental transfer of quetiapine in relation to P-glycoprotein activity

J Psychopharmacol. 2007 Sep;21(7):751-6. doi: 10.1177/0269881106074065. Epub 2007 Jan 26.

Abstract

Atypical antipsychotic drugs are well tolerated and thus often preferred in women of fertile age; yet the information on their placental transfer and use during the prenatal period is limited. The aim of this study was to study the placental transfer of quetiapine, a widely used atypical antipsychotic, with special reference to the role of the placental transporter protein, P-glycoprotein (P-gp). This was performed in 18 dually perfused placentas, using the well established P-gp inhibitors PSC833 (valspodar) and GG918 to inhibit the function of P-gp. We also aimed to clarify the significance of two potentially functional ABCB1 single nuclear polymorphisms (SNPs), 2677G>T/A and 3435C>T, on the transplacental transfer (TPT) of quetiapine. The placental transfer of quetiapine in the control group as measured by TPT(AUC) % (absolute fraction of the dose crossing placenta) was 3.7%, which is 29% less than the transfer of the freely diffusible antipyrine, which was 5.2%. The P-gp inhibitors had no significant effect on the transfer of quetiapine as measured by TPT(AUC) % (P = 0.77). No correlation was found between the transplacental transfer of quetiapine (TPT(AUC) %) and placental P-gp expression (P = 0.61). The 3435T allele in exon 26 was associated with significantly higher placental transfer of quetiapine (P = 0.04). We conclude that quetiapine passes the human placenta but that the blood-placental barrier partially limits the transplacental transfer of quetiapine. Administration of P-gp inhibiting drugs with quetiapine is not likely to increase fetal exposure to quetiapine, although the ABCB1 C3435T polymorphism may contribute to inter-individual variation in fetal exposure to quetiapine.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Acridines / pharmacology
  • Alleles
  • Antipsychotic Agents / pharmacokinetics*
  • Antipyrine / pharmacokinetics
  • Cyclosporins / pharmacology
  • Dibenzothiazepines / pharmacokinetics*
  • Drug Interactions
  • Exons
  • Female
  • Gene Expression
  • Genotype
  • Humans
  • Immunoblotting
  • In Vitro Techniques
  • Maternal-Fetal Exchange*
  • Perfusion
  • Placenta / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Quetiapine Fumarate
  • Tetrahydroisoquinolines / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Acridines
  • Antipsychotic Agents
  • Cyclosporins
  • Dibenzothiazepines
  • Tetrahydroisoquinolines
  • Quetiapine Fumarate
  • Elacridar
  • valspodar
  • Antipyrine