Lack of effect of chloroquine on the debrisoquine (CYP2D6 and S-mephenytoin (CYP2C19) hydroxylation phenotypes.
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.
Masimirembwa
C M
CM
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Gustafsson
L L
LL
Dahl
M L
ML
Abdi
Y A
YA
Hasler
J A
JA
D000328:Adult; D000962:Antimalarials / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D002738:Chloroquine / Q000494:pharmacology*; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism* / Q000652:urine; D010641:Phenotype; D013548:Sweden; D015030:Zimbabwe
D000962:Antimalarials; D002738:Chloroquine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6