Stable isotope methodology and gas chromatography mass spectrometry in a pharmacokinetic study of phenobarbital

A pharmacokinetic study of phenobarbital labeled with stable (nonradioactive) isotopes [1,3-15N, 2-13C] was conducted in patients undergoing chronic drug treatment for epilepsy. A pulse dose of stable isotope labeled phenobarbital was administered when plasma concentration of unlabeled phenobarbital was at a steady state. Plasma concentration-time profile of the labeled drug was obtained from serial blood samples using a gas chromatography mass spectrometry computer system. The data were used for pharmacokinetic analysis of the absorption, elimination and clearance of phenobarbital. Currently, this method is being used to study mechanisms of drug-drug interactions during antiepileptic therapy.