Pharmacokinetics of drugs in rabbits with experimental acute renal failure.

Serum protein binding and serum levels of antipyrine, phenytoin and phenylbutazone were measured in rabbits with acute renal failure induced by uranyl nitrate. The kinetics of antipyrine are not altered in the uraemic rabbit. Serum protein binding of phenytoin and phenylbutazone is decreased and the volume of distribution of total drug is increased. The volume of distribution of free phenytoin is unchanged, that of free phenylbutazone is decreased in acute renal failure. The half-lives of phenytoin and phenylbutazone are unchanged, but the serum clearance is increased in experimental acute renal failure. The intrinsic clearance of free drug, i.e. the ability of the liver enzymes to metabolize the drug, is not altered for antipyrine, is increased for phenytoin and is decreased for phenylbutazone. It is difficult to extrapolate these data obtained in rabbits with acute renal failure to humans in chronic renal failure.