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  • Title: Pharmacokinetics: dose-dependent changes.
    Author: Browne TR, Greenblatt DJ, Evans JE, Szabo GK, Evans BA, Schumacher GE.
    Journal: J Clin Pharmacol; 1986; 26(6):463-8. PubMed ID: 3734138.
    Abstract:
    Stable-isotope tracer methods are described for answering the following questions about a drug: Does the drug exhibit dose-dependent changes in pharmacokinetic properties? What are the drug's Michaelis constant (Km) and maximum velocity (Vmax) for enzymatic biotransformation; Are the dose-dependent pharmacokinetic changes great enough to be clinically important? and 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.
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