Abstract
Evidence from preclinical and clinical studies demonstrate that pregnancy is a physiological state capable of modifying drug disposition. Factors including increased hepatic metabolism and renal excretion are responsible for impacting disposition, and the role of membrane transporters expressed in biological barriers, including the placental- and blood-brain barriers, has received considerable attention. In this regard, the brain disposition of drugs in the mother and fetus has been the subject of studies attempting to characterize the mechanisms by which pregnancy could alter the expression of ATP-binding cassette (ABC) and solute carrier (SLC) transporters. This chapter will summarize findings of the influence of pregnancy on the maternal and fetal expression of ABC and SLC transporters in the brain and the consequences of such changes on the disposition of therapeutic drugs.
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Abbreviations
- ABC:
-
ATP-binding cassette
- AZT:
-
Zidovudine
- BBB:
-
Blood-brain barrier
- BCRP:
-
Breast cancer resistance protein
- BCSFB:
-
Blood-cerebrospinal fluid barrier
- CNT:
-
Concentrative nucleoside transporter
- CSF:
-
Cerebrospinal fluid
- ENT:
-
Equilibrative nucleoside transporter
- HIV:
-
Human immunodeficiency virus
- LAT:
-
L-alpha-amino acid transporter
- MCT:
-
Monocarboxylate transporter
- MRP:
-
Multidrug resistance-associated protein
- NRTI:
-
nucleoside reverse-transcriptase inhibitors
- OAT:
-
Organic anion transporter
- OATP:
-
Organic anion transporting polypeptide
- OCT:
-
Organic cation transporter
- P-GP:
-
P-glycoprotein
- Poly:IC:
-
polyinosinic:polycytidylic acid, PXR, Pregnane X receptor
- TGF:
-
Transforming growth factor
- TNF:
-
Tumor necrosis factor alpha
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The authors would like to acknowledge the support provided by the National Agency for Research and Development (Agencia Nacional de Investigacion y Desarrollo – ANID), through the grant REDI170373. Dr. Carlos Escudero is also supported by the ANID-FONDECYT grant 1200250.
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Torres-Vergara, P., Rivera, R., Escudero, C., Penny, J. (2023). Maternal and Fetal Expression of ATP-Binding Cassette and Solute Carrier Transporters Involved in the Brain Disposition of Drugs. In: Gonzalez-Ortiz, M. (eds) Advances in Maternal-Fetal Biomedicine. Advances in Experimental Medicine and Biology, vol 1428. Springer, Cham. https://doi.org/10.1007/978-3-031-32554-0_7
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