Distribution of antipyrine, phenylbutazone and phenytoin in experimental renal failure.

Concentrations of antipyrine, phenylbutazone and phenytoin were measured in serum and in tissues of rabbits with acute renal failure after uranyl nitrate injection, in view of our earlier finding that the volume of distribution of phenytoin and of phenylbutazone is increased in those animals. Concentrations of antipyrine in serum and in tissues were not altered in the uraemic rabbit. For phenylbutazone, total serum concentrations were decreased in uraemic rabbits; concentrations in brain, liver and fat were increased, while concentrations in other tissues and unbound serum concentrations were not significantly changed. For phenytoin, total serum concentrations were decreased and unbound serum concentrations and tissue concentrations were not significantly changed in uraemic rabbits. Calculation brain, liver and fat were increased, while concentrations in other tissues and unbound serum concentrations were not significantly changed. For phenytoin, total serum concentrations were decreased and unbound serum concentrations and tissue concentrations were not significantly changed in uraemic rabbits. Calculation brain, liver and fat were increased, while concentrations in other tissues and unbound serum concentrations were not significantly changed. For phenytoin, total serum concentrations were decreased and unbound serum concentrations and tissue concentrations were not significantly changed in uraemic rabbits. Calculation of the ratios of tissue concentrations over unbound serum concentrations suggests that the increased distribution volume of phenylbutazone and phenytoin in the uraemic rabbit is due to the decreased serum binding rather than to changes in tissue binding.