Placental transfer of quetiapine in relation to P-glycoprotein activity
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and PathologyDepartment of Medical Sciences2007 (English)In: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 21, no 7, 751-756 p.Article in journal (Refereed) Published
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 TPTAUC % (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 TPTAUC % (P = 0.77). No correlation was found between the transplacental transfer of quetiapine (TPTAUC %) 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.
Place, publisher, year, edition, pages
2007. Vol. 21, no 7, 751-756 p.
p-glycoprotein, ABCB1, MDR1, placental transfer
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-23780DOI: 10.1177/0269881106074065ISI: 000250515000010PubMedID: 17259208OAI: oai:DiVA.org:uu-23780DiVA: diva2:51554