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Placental transfer of quetiapine in relation to P-glycoprotein activity

Department of Pharmacology and Clinical Pharmacology, Joint Clinical Biochemistry Laboratory of University of Turku, Turku University Central Hospital, Turku, Finland, Department of Neurosurgery, Joint Clinical Biochemistry Laboratory of University of Turku, Turku University Central Hospital, Turku, Finland, melissa.rahi{at}tyks.fi

Tuija Heikkinen

Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland, Department of Obstetrics and Gynecology, University of Turku, Turku, Finland

Sebastian Härtter

Boehringer Ingelheim Pharma; Department of Drug Metabolism and Pharmacokinetics, Ingelheim, Germany

Jukka Hakkola

Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland

Kristo Hakala

Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland

Ola Wallerman

Department of Genetics and Pathology, Rudbeck, Uppsala University, Uppsala, Sweden

Mia Wadelius

Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden

Claes Wadelius

Department of Genetics and Pathology, Rudbeck, Uppsala University, Uppsala, Sweden

Kari Laine

Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland

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.

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

This version was published on September 1, 2007

Journal of Psychopharmacology, Vol. 21, No. 7, 751-756 (2007)
DOI: 10.1177/0269881106074065


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