Chapter 24 Stable isotope techniques in drug development: An economic evaluation

Abstract

This chapter presents an economic evaluation of stable isotope labeled (SIL) techniques in drug development. This evaluation covers two areas: (1) use of SIL methods to perform single studies required for Phase I; and (2) use of SIL methods to perform multiple studies required for Phase I, including combining two or more studies into a single more efficient study. When used for a single study, SIL methods are least efficient economically. However, by performing several studies with SIL tracers, start-up costs are spread over several studies, and the potential cost savings with SIL methods can be better exploited. Mass balance/metabolite identification studies have been performed by: (1) administering radioactive ( 14 C)-labeled drug, (2) measurement of radioactivity in urine and feces, (3) chromatography of urine to divide dissolved material into peaks, (4) recognition of peaks containing drug or metabolite by presence of radioactivity, and (5) identification of structure of drug or metabolite in “hot” peaks by mass spectrometry (MS). The overall cost of a mass balance/metabolite identification study performed with SlL- or 14 C-labeling is approximately equal. Multiple-dose volunteer studies are performed to determine the type of pharmacokinetic properties (linear, concentration-, or time-dependent) and the pharmacokinetic values (clearance, half-life dependent, volume of distribution) a new drug has during chronic administration and to obtain information on safety during long term administration.