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Obtaining pharmacokinetic data from the intravenous route for drugs intended for oral administration has traditionally been expensive and time consuming because of the toxicology requirements and challenges in intravenous formulations. Such studies are necessary, however, particularly when regulator agencies request absolute bioavailability data. A method has emerged whereby the drug administered intravenously is isotopically labeled and dosed at a maximum of 100 μg concomitantly with an oral administration given at a therapeutically relevant level. The intravenous administration has been termed a microtracer and obviates intravenous toxicology requirements as well as simplifying formulations. The study design also essentially removes issues of nonlinear pharmacokinetics that may occur when oral and intravenous doses are administered separately. This review examines the methodology and the literature to date, including those studies intended for regulatory submission. The method has been extended to the study of prodrug–to–active drug kinetics and to obtaining clearance, volume of distribution, and absolute bioavailability at steady-state conditions.