Deuterium isotope effects in studies of drug metabolism

Abstract

Substitution of one or more carbon-bonded hydrogen atoms in a drug molecule with deuterium imposes negligible steric effects and influences physio-chemical properties minimally. Yet the resultant increased bond stability may cause dramatic changes in biological properties, particularly by retarding certain pathways of its metabolism. Allan Foster describes the potential of deuteration in modifying drug action. A specific biological action of a drug may be enhanced, reduced or prolonged; its metabolism may be diverted along a pathway which promotes formation of highly active metabolites, or avoids the formation of toxic metabolites. So why have deuterium isotope effects (DIEs) not been exploited? Cost of toxivology testing and clinical trials may underline the pharmaceutical industry's reluctance to synthesize deuterated analogues. Nonetheless, deuteration remains a promising possibility for future drug design. © 1984.