TY - JOUR
T1 - Effect of experimental hypoalbuminemia on the plasma protein binding of tolmetin
AU - Pérez-Urizar, José
AU - Flores-Murrieta, Francisco J.
AU - Castaeda-Hernández, Gilberto
PY - 2002/7/19
Y1 - 2002/7/19
N2 - The purpose of this work was to study tolmetin plasma protein binding in an experimental model of hypoalbuminemia in the rat. Hypoalbuminemia was produced by repetitive plasmapheresis, achieving a 26.2 ± 4.6% reduction in albumin circulating levels. Rats then received a 100 mg/kg oral tolmetin dose. Control rats received oral tolmetin 10, 56 or 100 mg/kg. Tolmetin plasma protein binding was determined by an ultrafiltration technique using an in vivo pharmacokinetic approach. Plasma protein binding data for the 3 doses studies in control animals could be described considering a single binding site with Kd = 21.9 ± 2.1 μM and N = 0.98 ± 0.05 sites per molecule of albumin. For hypoalbuminemic rats Kd was significantly increased (p < 0.05), while there was no significant change in the number of binding site per albumin molecule (Kd = 131.6 ± 38.1 μM and N = 1.58 ± 0.77). Our results show that hypoalbuminemia produces a disproportionate increase in the free fraction of tolmetin, not only by reducing albumin concentration, but also by a decrease in affinity. The mechanism responsible of such changes in affinity remains to be elucidated.
AB - The purpose of this work was to study tolmetin plasma protein binding in an experimental model of hypoalbuminemia in the rat. Hypoalbuminemia was produced by repetitive plasmapheresis, achieving a 26.2 ± 4.6% reduction in albumin circulating levels. Rats then received a 100 mg/kg oral tolmetin dose. Control rats received oral tolmetin 10, 56 or 100 mg/kg. Tolmetin plasma protein binding was determined by an ultrafiltration technique using an in vivo pharmacokinetic approach. Plasma protein binding data for the 3 doses studies in control animals could be described considering a single binding site with Kd = 21.9 ± 2.1 μM and N = 0.98 ± 0.05 sites per molecule of albumin. For hypoalbuminemic rats Kd was significantly increased (p < 0.05), while there was no significant change in the number of binding site per albumin molecule (Kd = 131.6 ± 38.1 μM and N = 1.58 ± 0.77). Our results show that hypoalbuminemia produces a disproportionate increase in the free fraction of tolmetin, not only by reducing albumin concentration, but also by a decrease in affinity. The mechanism responsible of such changes in affinity remains to be elucidated.
KW - Experimental hypoalbuminemia
KW - Protein-binding
KW - Tolmetin
UR - http://www.scopus.com/inward/record.url?scp=0037135263&partnerID=8YFLogxK
U2 - 10.1016/S0024-3205(02)01788-5
DO - 10.1016/S0024-3205(02)01788-5
M3 - Artículo
SN - 0024-3205
VL - 71
SP - 1015
EP - 1022
JO - Life Sciences
JF - Life Sciences
IS - 9
ER -