RT info:eu-repo/semantics/preprint
T1 Abcg2 transporter affects plasma, milk and tissue levels of meloxicam
A1 Garcia-Lino, Alba Maria
A1 Blanco Paniagua, Esther
A1 Astorga-Simon, Elsa N.
A1 García Mateos, Dafne
A1 Alvarez-Fernandez, Indira
A1 Álvarez de Felipe, Ana Isabel
A1 Merino Peláez, Gracia
A2 Fisiologia
K1 Fisiología
K1 ABCG2
K1 Leche
K1 Meloxicam
K1 Plasma
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 and secretion 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 is an 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, with a 20-fold higher concentration in the brain of Abcg2-/- compared to wild-type mice. Meloxicam secretion into milk was also affected by the transporter, with a 2.5-fold higher milk-to-plasma ratio in wild-type compared with Abcg2-/- lactating female mice (0.58 ± 0.08 versus 0.23 ± 0.06). 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.This study was supported by the research projects AGL2015-65626-R (MINECO/FEDER, UE) and RTI2018-100903-B-I00 (AEI/FEDER, UE); and by the predoctoral grants from the Ministry of Economy, Industry and Competitiveness (BES-2016-077235 grant to AMGL), and from Spanish Ministry of Education, Culture and Sport (FPU14/05131 grant to DGM AND FPU18/01559 grant to EBP); and the Junta de Castilla y Leon and European Regional Development Fund (Post-Doctoral Fellowship LE011P17 grant to IAF).
PB Elsevier
SN 0006-2952
LK http://hdl.handle.net/10612/12328
UL http://hdl.handle.net/10612/12328
NO 33 p.
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 20-abr-2024