Effect of experimental hypoalbuminemia on the plasma protein binding of tolmetin |
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Authors: | Pérez-Urizar José Flores-Murrieta Francisco J Castañeda-Hernández Gilberto |
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Institution: | Sección Externa de Farmacología, CINVESTAV-IPN, Av. IPN No. 2508. San Pedro Zacatenco, D.F. 07360, México, Mexico. jpurizar@uaslp.mx |
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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. |
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Keywords: | Tolmetin Protein-binding Experimental hypoalbuminemia |
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