Effect of induced hypoalbuminemia on distribution, total clearance and unbound clearance of Piroxicam in vivo in the rat

Abstract

The influence of decreased albumin concentration on the pharmacokinetic behaviour of Piroxicam was studied in vivo in rats that had undergone plasmapheresis. Reductions of approximately 25% and 50% in the plasma albumin concentration were achieved, the former in rats not given plasma expander, the latter in animals given Ficol-70 as a plasma expander. The unbound fraction of Piroxicam in plasma and the apparent volume of distribution at steady state experienced a statistically significant increase where the albumin concentration was reduced. The average total plasma clearance rose with the increase in fu, between the control (6.3 +/- 2.4 ml/h) and plasmapheretic groups (11.1 +/- 4 ml/h), in accordance with predictions of the 'well-stirred' and 'parallel-tube' models, but no statistically significant differences were found between the two groups, perhaps because of the great interindividual variability associated with this parameter. The total plasma clearance value of the Ficol group (5.4 +/- 2.2 ml/h) was close to that of the control group, despite the high increase in the unbound fraction in plasma. Alterations in the uptake process in the liver due to the high level of induced hypoalbuminemia may have occurred.

Multi‐phase multi‐layer mechanistic dermal absorption (MPML MechDermA) model to predict local and systemic exposure of drug products applied on skin

“…The B:P partition ratio was calculated based on rat data, 71 corrected for hematocrit and plasma binding. Volume of distribution values from [72][73][74][75] were 0.31, 0.15, 0.12, and 0.14 L/kg, respectively.…”