PMID: 1361533Nov 1, 1992Paper

Effect of uraemia and anephric state on the pharmacokinetics of tenoxicam in the rat

The Journal of Pharmacy and Pharmacology
L G Lopez-BustamanteD Fos


Renal alterations, uraemia and nephrotic syndrome induced in experimental animals caused a reduction in the plasma albumin concentration of 25 and 30%, respectively. As a result of this decrease, the unbound fraction of tenoxicam in uraemic rats (0.06 +/- 0.02) and in anephric rats (0.11 +/- 0.08) increased with respect to the control group (0.03 +/- 0.004). The induced hypoalbuminaemia did not modify the blood to plasma concentration ratio. Both plasma clearance (CL) and apparent volume of distribution at steady-state (Vdss) rose significantly with the increase in the unbound fraction: (Vdss 55 +/- 6 mL (control rats); 69 +/- 12 mL (uraemic rats); 96 +/- 30 mL (anephric rats); CL = 7 +/- 1 mL h-1 (control rats); 12 +/- 4 mL h-1 (uraemic rats); 15 +/- 7 mL h-1 (anephric rats)). Tenoxicam elimination was found to be restrictive, with an extraction ratio less than 0.1 in the three groups. The induction of nephrotic syndrome was observed to have a significant effect on intrinsic metabolic activity, intrinsic clearance of tenoxicam being reduced by 30% in the anephric rats (161 +/- 38 mL h-1) with respect to the values obtained in the control group (228 +/- 22 mL h-1).


Jan 1, 1976·Clinical Pharmacokinetics·R Gugler, D L Azarnoff
Jan 1, 1990·European Journal of Clinical Pharmacology·C BenvenisteP Dayer
Oct 1, 1988·British Journal of Clinical Pharmacology·R O DayD N Wade
Jan 1, 1988·European Journal of Clinical Pharmacology·O G NilsenE Thue
Sep 1, 1972·Kidney International·H W Leber, G Schütterle
Jan 1, 1971·Clinica Chimica Acta; International Journal of Clinical Chemistry·B T DoumasH G Biggs
Jan 1, 1982·Clinical Pharmacokinetics·S WanwimolrukP M Brooks
Feb 1, 1981·Journal of Pharmaceutical Sciences·K M GiacominiG Levy

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