Lack of effect of chloroquine on the debrisoquine (CYP2D6) and S‐mephenytoin (CYP2C19) hydroxylation phenotypes

Abstract

The effects of chloroquine (CHQ) on debrisoquine hydroxylase (CYP2D6) and S‐mephenytoin hydroxylase (CYP2C19) were assessed in 11 black Zimbabwean and 12 white Swedish healthy volunteers. The activity of CYP2D6 was measured as the urinary debrisoquine to 4‐hydroxydebrisoquine metabolic ratio and that of CYP2C19 as the urinary S‐ to R‐mephenytoin enantiomer ratio (S/R). There were no statistically significant differences in either metabolic ratio as a result of prophylactic or loading doses of CHQ. This indicates that CHQ does not inhibit CYP2D6 or CYP2C19 in vivo and is unlikely to compromise the metabolism of substrates for these two enzymes. It is, therefore, also unlikely that residual CHQ in populations under study will interfere with phenotyping of either CYP2D6 or CYP2C19.