Approaches to intravenous clinical pharmacokinetics: Recent developments with isotopic microtracers

Abstract

Obtaining pharmacokinetic data from the intravenous (i.v.) route for drugs intended for oral administration has traditionally been expensive and time consuming because of the toxicology requirements and challenges in i.v. formulation. Such studies are necessary however, particularly when regulator agencies request absolute bioavailability data. A method has emerged whereby the drug administered i.v. is isotopically labeled and dosed at a maximum of 100 µg concomitantly with an oral administration given at a therapeutically‐relevant level. The i.v. administration has been termed a microtracer and obviates i.v. toxicology requirements as well as simplifying formulation. The study design also essentially removes issues of non‐linear pharmacokinetics that may occur when oral and i.v. 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 pro‐drug to active drug kinetics and to obtaining clearance, volume of distribution and absolute bioavailability at steady state conditions. This article is protected by copyright. All rights reserved