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Pharmacokinetics: Dose‐Dependent Changes
Author(s) -
Browne Thomas R.,
Greenblatt David J.,
Evans James E.,
Szabo George K.,
Evans Barbara A.,
Schumacher Gerald E.
Publication year - 1986
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1986.tb03559.x
Subject(s) - pharmacokinetics , biotransformation , drug , pharmacology , chemistry , phenobarbital , medicine , enzyme , biochemistry
Stable‐isotope tracer methods are described for answering the following questions about a drug: (1) Does the drug exhibit dose‐dependent changes in pharmacokinetic properties? (2) What are the drug's Michaelis constant (K m ) and maximum velocity (V max ) for enzymatic biotransformation; (3) Are the dose‐dependent pharmacokinetic changes great enough to be clinically important? and (4) Which routes of the drug's biotransformation are responsible for the drug's dose‐dependent pharmacokinetic properties? Illustrative data are provided from tracer studies performed with a drug with dose‐dependent pharmacokinetic properties, phenytoin, and a drug that does not exhibit dose‐dependent pharmacokinetic properties, phenobarbital. The advantages and disadvantages of the described stable‐isotope methods are discussed.