Characterization of P-glycoprotein orthologs from human, sheep, pig, dog, and cat

The ATP-binding cassette transporter P-glycoprotein (P-gp) limits the oral bioavailability of many drugs. Although P-gp has been well studied in humans and mice, little is known about the substrate specificities of many of its species orthologs. To address this, we performed in vitro analysis of P-g...

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Veröffentlicht in:Journal of veterinary pharmacology and therapeutics 2023-11, Vol.46 (6), p.401-412
Hauptverfasser: Azimi, Mina, Yee, Sook Wah, Riselli, Andrew, Silva, Dina Buitrago, Giacomini, Craig P, Giacomini, Kathleen M, Brett, Claire M
Format: Artikel
Sprache:eng
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Zusammenfassung:The ATP-binding cassette transporter P-glycoprotein (P-gp) limits the oral bioavailability of many drugs. Although P-gp has been well studied in humans and mice, little is known about the substrate specificities of many of its species orthologs. To address this, we performed in vitro analysis of P-gp transporter function using HEK293 cells stably expressing human, ovine, porcine, canine, and feline P-gp. We also employed a human physiologically based pharmacokinetic (PBPK) model to assess variations in digoxin exposure resulting from altered P-gp function. Compared to human P-gp, sheep P-gp had significantly less digoxin efflux (2.3-fold ±0.04 vs. 1.8-fold ±0.03, p 
ISSN:0140-7783
1365-2885
DOI:10.1111/jvp.13386