Assessment of urinary mephenytoin metrics to phenotype for CYP2C19 and CYP2B6 activity

Objectives (S)-Mephenytoin is selectively metabolised to (S)-4′-hydroxymephenytoin by CYP2C19. The urinary excretion of 4′-hydroxymephenytoin reflects the activity of individual enzymes. We evaluated fractioned urinary collection and β-glucuronidase pre-treatment in order to determine the optimal CYP2C19 metrics. We also assessed whether urinary excretion of N-desmethylmephenytoin (nirvanol) might be a useful CYP2B6 metric in in vivo studies.