Effect of uraemia and anephric state on the pharmacokinetics of tenoxicam in the rat.
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).
Departamento Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain.
L G
LG
Lopez-Bustamante
J I
JI
Troconiz
D
D
Fos
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009392:Nephrectomy; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D014511:Uremia / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D012709:Serum Albumin; D010894:Piroxicam; C032801:tenoxicam