Diphenylhydantoin Metabolism in Uremia

Pharmacokinetics of drugs in patients with the nephrotic syndrome.

“…or CPIB/CPIB glucuronide ratio in the DISCUSSION It is well recognized that in uremic patients DPH steady-state concentrations are lower than in normal volunteers (2,13,14). The decreased binding in this disease appears to be related to inherent alteration in the plasma proteins (3) whereas a change in the protein concentration per se seems to be of minor importance (2).…”

Pharmacokinetics of Drugs in Rabbits with Experimental Acute Renal Failure

“…For phenytoin (15,20) and warfarin (1), a shortened half-life was reported. For aminophenazone (14), pentobarbital (24), phenacetin (21) and tolbutamide (9), the halflife was found to be unchanged.…”

“…The changes in half-life found in man or in animals are often explained by changes in he patic metabolism (1,10,14,15,18,20,25,27), but in vitro studies showed a tendency to a decrease in activity o f the hepatic microsomal enzymes in rats with acute renal failure (12,13,19,28). However, the possibility that in some instances, the half-life is shortened by the decreased serum protein binding in renal failure (2, 23) has been forwarded (10,15,20).…”

“…However, the possibility that in some instances, the half-life is shortened by the decreased serum protein binding in renal failure (2, 23) has been forwarded (10,15,20).…”

Impact of Severe Sepsis or Septic Shock on Drug Response

“…Both drugs are bound to albumin: 50% and 90% for vancomycin and phenytoin respectively. Vancomycin is mainly excreted by the kidneys (80%), whereas hepatic metabolism is predominant for phenytoin with less than 5% excreted as unchanged drug in the urine (Letteri et al, 1971). CYP2C9 and CYP2C19 are the main enzymes responsible for phenytoin elimination (Levy, 1995) and their low distribution in the gut suggests an hepatic metabolism for this drug (Läpple et al, 2003).…”