Placental transfer of quetiapine in relation to P-glycoprotein activity

¹ Department of Pharmacology and Clinical Pharmacology, Department of Neurosurgery, Joint Clinical Biochemistry Laboratory of University of Turku, Turku University Central Hospital, Turku, Finland.
² Department of Pharmacology and Clinical Pharmacology, Department of Obstetrics and Gynecology, University of Turku, Turku, Finland.
³ Boehringer Ingelheim Pharma; Department of Drug Metabolism and Pharmacokinetics, Ingelheim, Germany.
⁴ Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland.
⁵ Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
⁶ Department of Genetics and Pathology, Rudbeck, Uppsala University, Uppsala, Sweden.
⁷ Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden.

^* To whom correspondence should be addressed.

	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.

Key Words: P-glycoprotein, placenta, quetiapine, ABCB1 polymorphism

First published on January 26, 2007, doi:10.1177/0269881106074065

Journal of Psychopharmacology 2007;21:751.

A more recent version of this article appeared on September 1, 2007


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