Use of stable isotopes in pharmacology‐clinical pharmacology

Abstract

The greatest advantages offered by stable isotopes over their radioactive counterparts is the absence of problems associated with radiation. Absence of possible radiation damage to living systems is very important in human studies, especially in the case of children or pregnant women. Absence of radiation hazard also makes the synthesis and handling of stable isotope‐labeled compounds much simpler.

The Neurochemical Basis of Acetylcholine Precursor Loading as a Therapeutic Strategy

“…TItis is an area in which isotopic tracers will be required, and deuterium-labelled Ch has proven to be valuable in experimental studies of this kind (Hanin and Schuberth, 1974;Choi et ai., 1975;Freeman et al, 1975;Schuberth and lenden, 1975). Hazards from the clinical use of stable isotopes are minimal (Knapp and Gaffney, 1972;lenden, 1978), although the use of 13C instead of 2H might be a wise precaution to eliminate the possibility of significant isotope effects. Following experimental designs which have already been established in laboratory animals, this could yield information about the kinetics of formation, transport and utilization of free and esterified forms of Ch, which is badly needed in the human subject.…”

Stable isotopes in drug metabolism and pharmacokinetics

“…This required the purification and the combustion of the sample prior to the analyses (12). The GCjMS techniques, first used by Henneberg in 1959 (5, 6) and Sweeley et al (1965) (13), often allow the stages of purification and combustion to be dropped.…”

“…The main advantage of this technique is that it requires extremely small samples since the recording of the whole spectrum of a molecule is no longer necessary. In fact the identification is based on the retention time and the ratio of the preselected ions whereas quantitative determinations, down to the picogram level, are achieved by measuring the intensities of these ions (12).…”

“…This difficulty may be overcome by an adequate labelling of the molecule with one or several stable isotopes. The mixture of the labelled and unlabelled compound then generates typical clusters separated only by some mass units (12).…”

“…Current labelling of drugs by radioactive isotopes cannot be used for determination by MF. The abundance of these isotopes is indeed too small to give rise to easily detectable ion groups (12,14). Nevertheless some authors (30) using particularly high specific radioactivities have been able to exploit radioactive isotopes for such a purpose.…”