Stable Isotope Methodology in Bioavailability/Pharmacokinetic Research

Abstract

The use of stable isotopically labeled drugs combined with gas chromatographymass spectrometry (GC-MS) has found a broad application in pharmacological studies. Initially, stable isotopically labeled drugs and metabolites served as the ideal mass internal standards for analytic procedures. However, their in vivo use has expanded and proved to be a powerful pharmacokinetic tool. This review article will emphasize the utilization of stable isotope methodology in studying the bioavailability/pharmacokinetic of drugs. The primary advantage of the isotopic methods is that the drug can be administered concomitantly either by two routes (e.g., intravenous and oral) or in two formulations (e.g., solution and solid dosage). Thus, a single set of blood samples serves to describe the time course to the routes or formulations being compared. The technigue is also well suited to “pulse”administration, wherein the kinetics of a single dose, during chronic dosing regimens, canbe examined. Another major advantage of the technique is that endogenous and exogenous compounds having the same basic structure can be differentiated by employing stable isotopically labeled analogs. I will attempt to outline the elements of study design for the application of stable isotope methodology.