Cellular Uptake of Levocetirizine by Organic Anion Transporter 4.

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Noguchi S, Nishimura T, Mukaida S, Benet LZ, Nakashima E, Tomi M

Cellular Uptake of Levocetirizine by Organic Anion Transporter 4.

J Pharm Sci. 2017 Sep;106(9):2895-2898. doi: 10.1016/j.xphs.2017.03.026. Epub 2017 Apr 4.

PubMed ID

28385546 [ View in PubMed

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Abstract

The pharmacokinetics of cetirizine, a nonsedating antihistamine, is profoundly affected by transporter-mediated membrane transport in the kidney. In this study, we aimed to investigate the transport mechanism of levocetirizine, the pharmacologically active enantiomer of cetirizine, via human organic anion transporter 4 (OAT4) expressed in the apical membrane of renal proximal tubules and the basal plasma membrane of placental syncytiotrophoblasts. In cells expressing human OAT4 under the control of tetracycline, levocetirizine uptake was increased by tetracycline treatment. On the other hand, OAT4 expression did not facilitate efflux of preloaded levocetirizine from the cells, either in the presence or absence of extracellular Cl(-). The OAT4-mediated levocetirizine uptake was concentration-dependent with a Km of 38 muM. The uptake rate of levocetirizine via OAT4 was approximately twice that of racemic cetirizine, indicating stereoselective uptake of levocetirizine. On the other hand, OAT4-mediated [(3)H]dehydroepiandrosterone sulfate uptake was inhibited by dextrocetirizine and levocetirizine. Overall, our findings indicate that OAT4 mediates levocetirizine uptake but is unlikely to mediate the efflux.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Levocetirizine	Solute carrier family 22 member 11	Protein	Humans	Unknown	Substrate	Details