title: Pharmacokinetics: dose-dependent changes.
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.
mesh_terms: D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism* / Q000652:urine; D010634:Phenobarbital / Q000378:metabolism / Q000494:pharmacology; D010672:Phenytoin / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations; D010672:Phenytoin; D010634:Phenobarbital