Biomedical subjects
T R Browne
Publications and source records attributed to T R Browne.
Pharmacokinetics: dose-dependent changes.
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.
Stable isotopes in pharmacology studies: present and future.
Stable-isotope techniques offer advantages over older methods in safety, sensitivity, specificity, and reduction in numbers of subjects required and analytic determinations for some types of pharmacology studies. In addition to their use as internal standards in gas chromatography-mass spectrometry analytic methods, stable isotopes have been successfully employed in studies of absorption, bioavailability, distribution, biotransformation, excretion, metabolite identification, time-dependent and dose-dependent pharmacokinetic changes, drug interactions, pharmacologic changes during pregnancy, mutagenicity, and teratogenicity.