Relationship between mephenytoin, phenytoin and tolbutamide hydroxylations in healthy African subjects

Mephenytoin, phenytoin and tolbutamide are metabolised by the cytochrome P-450 (CYP) 2C family. Recently, it has been shown that phenytoin and tolbutamide are metabolised by CYP2C9/10 whereas mephenytoin is metabolised by CYP2C19. Until now, in vivo studies were only undertaken in Caucasian subjects and showed a strong relationship between phenytoin and tolbutamide metabolism but no significant relationship between the two drug metabolisms and that of mephenytoin. The metabolism of the three drugs was investigated in eight black Africans by urinary analysis. In this ethnic group, a strong relationship was found between phenytoin and tolbutamide oxidations (rs = -0.83, P = 0.01). On the other hand, no significant relationship was found between mephentoin oxidation and phenytoin or tolbutamide oxidations (rs = 0.31 and rs = -0.33, respectively). This study suggests that, in black Africans, phenytoin and tolbutamide but not mephenytoin are also hydroxylated by similar CYP enzyme(s).