Metabolic switching of drug pathways as a consequence of deuterium substitution

An investigation was made of the metabolism of deuterated analogs of caffeine (1-CD3-caffeine and 7-CD3-caffeine) and antipyrine (N-CD3-antipyrine and 3-CD3-antipyrine) because both caffeine and antipyrine are metabolized by multiple alternate pathways. Since it is well established that carbon-deuterium bonds are more stable than carbon-hydrogen bonds, it was postulated that oxidation of the CD3 group would be depressed and that metabolism of the labeled compounds would be shifted to another pathway that did not involve cleavage of a carbon-deuterium bond. Metabolic switching of drug pathways was observed in vivo for both of the caffeine analogs and was observed both in vivo and in vitro for 3-CD3-antipyrine