RT info:eu-repo/semantics/article
T1 Abcg2 transporter affects plasma, milk and tissue levels of meloxicam
A1 García Lino, Alba María
A1 Blanco Paniagua, Esther
A1 Astorga-Simon, Elsa N.
A1 Álvarez Fernández, Laura
A1 García Mateos, Dafne
A1 Alvarez-Fernandez, Indira
A1 Álvarez de Felipe, Ana Isabel
A1 Merino Peláez, Gracia
A2 Fisiologia
K1 Farmacología
K1 ABCG2
K1 meloxicam
K1 membrane transport
K1 pharmacokinetics
K1 tissue distribution
AB ATP-binding cassette (ABCG2) is an efflux transporter that extrudes xenotoxins from cells in liver, intestine, mammary gland, brain and other organs, affecting the pharmacokinetics, brain accumulation andsecretion into milk of several compounds, including antitumoral, antimicrobial and anti-inflammatory drugs. The aim of this study was to investigate whether the widely used anti-inflammatory drug meloxicam isan Abcg2 sustrate, and how this transporter affects its systemic distribution. Using polarized ABCG2-transduced cell lines, we found that meloxicam is efficiently transported by murine Abcg2 and human ABCG2. After oral administration of meloxicam, the area under the plasma concentration-time curve in Abcg2-/- mice was 2-fold higher than in wild type mice (146.06 ± 10.57 μg·h/ml versus 73.80 ± 10.00 μg·h/ml). Differences in meloxicam distribution were reported for several tissues after oral and intravenous administration, with a 20-fold higher concentration in the brain of Abcg2-/- after oral administration.Meloxicam secretion into milk was also affected by the transporter, with a 2-fold higher milk-to-plasma ratio in wild-type compared with Abcg2-/- lactating female mice after oral and intravenous administration. We conclude that Abcg2 is an important determinant of the plasma and brain distribution of meloxicam and is clearly involved in its secretion into milk.
PB Elsevier
SN 1873-2968, 0006-2952
LK https://hdl.handle.net/10612/17443
UL https://hdl.handle.net/10612/17443
NO Garcia-Lino, A. M., Blanco-Paniagua, E., Astorga-Simon, E. N., Alvarez-Fernandez, L., Garcia-Mateos, D., Alvarez-Fernandez, I., Alvarez, A. I., & Merino, G. (2020). Abcg2 transporter affects plasma, milk and tissue levels of meloxicam. Biochemical Pharmacology.
NO https://doi.org/10.1016/j.bcp.2020.113924
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 20-may-2024