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Stable isotope labeled tracer doses of phenytoin (PHT) and phenobarbital (PB) were given intravenously before and four and 12 weeks after beginning monotherapy in two groups of six patients. Phenytoin demonstrated nonlinear pharmacokinetics, while PB demonstrated linear pharmacokinetics. Each of the 36 sets of tracer dose serum concentration versus time data points appeared linear during the elimination phase on semilog plots, and each demonstrated a high degree of linearity using semilog regression analysis (r2 = .977-.999, P less than .001, for PHT; r2 = .791-.996, P less than .005, for PB). We conclude tracer doses administered at steady-state serum concentration will exhibit linear serum concentration versus time relationships on semilog plots regardless of whether the steady-state serum concentration is in the linear or the nonlinear portion of a drug's dose versus steady-state serum concentration relationship. The mechanism and implications of this conclusion are discussed.
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
January 2007,
Radiation protection dosimetry,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
January 1986,
Journal of clinical pharmacology,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
November 1995,
Protein science : a publication of the Protein Society,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
August 1947,
Bulletin. Chicago Medical Society,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
May 1948,
Nature,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
July 1996,
Drug metabolism and disposition: the biological fate of chemicals,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
December 1948,
The Analyst,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
June 2001,
Seminars in perinatology,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
September 1973,
Biochemical pharmacology,
T R Browne, and
D J Greenblatt, and
J S Harmatz, and
J E Evans, and
G K Szabo, and
B A Evans, and
G E Schumacher
March 1981,
Science (New York, N.Y.),
