Proguanil metabolism is determined by the mephenytoin oxidation polymorphism in Vietnamese living in Denmark.
1. A sparteine/mephenytoin phenotyping test was carried out in 37 Vietnamese living in Denmark. By visual inspection the urinary S/R-mephenytoin ratio appeared to show a bimodal frequency distribution. Eight putative poor metabolizers of mephenytoin, PMm (22%), had S/R-mephenytoin ratios from 0.79 to 1.12 and 29 putative extensive metabolizers of mephenytoin, EMm, had S/R-mephenytoin ratios < or = 0.55. All of the subjects were extensive metabolizers of sparteine with urinary metabolic ratios from 0.15 to 2.4. 2. The metabolism of the antimalarial prodrug proguanil was studied in 34 of the subjects after a single oral dose of 100 mg. The median 12 h urinary recoveries of the active metabolite cycloguanil and the minor metabolite 4-chlorphenylbiguanide were 5.8 and 1.9% of the dose, respectively, in 26 EMm compared with 1.6 and 0.4%, respectively, in 8 PMm (P < 0.001, Mann-Whitney U-test). 3. There was no statistically significant correlation (Spearmans rs) between any index of proguanil metabolism and the sparteine metabolic ratio.
Department of Clinical Pharmacology, Odense University, Denmark.
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Brøsen
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Skjelbo
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Flachs
D000284:Administration, Oral; D000328:Adult; D001645:Biguanides / Q000652:urine; D003718:Denmark; D005260:Female; D006801:Humans; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D002727:Proguanil / Q000008:administration & dosage / Q000378:metabolism*; D013034:Sparteine / Q000378:metabolism; D014227:Triazines / Q000652:urine; D014744:Vietnam / Q000208:ethnology
D001645:Biguanides; D014227:Triazines; C026009:cycloguanil; D013034:Sparteine; C025963:4-chlorophenylbiguanide; D008617:Mephenytoin; D002727:Proguanil