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Unexpectedly low serum phenytoin levels occurred in burned epileptic patients, suggesting the possibility of altered phenytoin disposition. Subsequently, phenytoin log-linear elimination kinetics after a 10 mg/kg i.v. single dose was examined in a burned rat model. Clearance increased from 1.08 +/- 0.28 liters/hr/kg in control rats to 1.50 +/- 0.38 liters/hr/kg in burned rats (P less than .05). The volume of distribution increased from 0.82 +/- 0.058 liters/kg in control rats to 1.01 +/- 0.11 liters/kg in burned rats (P less than .0005). The first order elimination rate constant (KE) did not change significantly (1.31 +/- 0.37) hr-1 in control rats vs. 1.52 +/- 0.48 hr-1 in burned rats; P greater than .05). The increase in clearance and in volume of distribution could be explained on the basis of a decrease in plasma protein binding. The free fraction in plasma increased from 27.1% +/- 1.2 in controls to 33.4% +/- 1.6 in burned rats (P less than .0005). The change in binding was consistent with a decrease in serum albumin from 2.64 +/- 0.33 g/dl in controls to 1.98 +/- 0.16 g/dl in burned rats (P less than .0005). Plasma samples of four burned human subjects revealed low serum albumin and markedly decreased plasma protein binding of phenytoin (2- to 3-fold increase in free fraction in plasma).
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
August 1982,
British journal of clinical pharmacology,
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
September 2022,
Antibiotics (Basel, Switzerland),
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
January 1977,
Clinical pharmacokinetics,
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
December 1979,
British journal of clinical pharmacology,
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
March 2016,
Drug research,
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
March 1998,
Drug metabolism and disposition: the biological fate of chemicals,
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
July 1987,
Sheng li ke xue jin zhan [Progress in physiology],
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
May 1985,
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
April 2014,
Molecules (Basel, Switzerland),
T A Bowdle, and
G D Neal, and
R H Levy, and
D M Heimbach
April 1986,
The Indian journal of medical research,
