title: Effect of experimental hypoalbuminemia on the plasma protein binding of tolmetin.
abstract: 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 microM 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 microM 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.
authors.affiliation: Sección Externa de Farmacología, CINVESTAV-IPN, Av. IPN No. 2508. San Pedro Zacatenco, D.F. 07360, México, Mexico. jpurizar@uaslp.mx
authors.forename: José
authors.initials: J
authors.lastname: Pérez-Urizar
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Flores-Murrieta
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
mesh_terms: D000818:Animals; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D014046:Tolmetin / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D012709:Serum Albumin; D014046:Tolmetin