Role of the red blood cell in drug metabolism

Contrary to the belief that the RBC is not metabolically active towards pharmacologically active endogenous and exogenous substances, it is evident that the RBC contains moderate cytochrome P-450-like activity, in addition to the ability to catalyse various other transformations of a range of drugs. The list of drugs for which there is evidence of metabolism by RBC (Table 1) contains examples from several drug classes. However some major classes of drugs which are principally cleared in vivo by metabolism are missing (for example, benzodiazepines). Moreover, there is as yet no evidence for the RBC having the capacity for the more important drug conjugation reactions (glucuronidation, sulphation) although there is evidence of other conjugation reactions (methylation, acetylation, glutathione conjugation). It is conceivable that the RBC could be used as a convenient tissue to add to other metabolism screening procedures used in drug development. Already use has been made of the RBC in identifying fast and slow acetylators. Others have used RBC to identify a possible sex-based difference in drug metabolism. Hopefully, this review has stimulated interest in the ability of the RBC to metabolize drugs and this interest will result in further discoveries.