Association between CYP2C19 genotype and proguanil oxidative polymorphism.
OBJECTIVE
To examine the relationship between proguanil metabolism and the number of mutations in CYP2C19 by comparing the CYP2C19 genotype and proguanil phenotype of 10 subjects.


METHODS
Partial clearance and urinary metabolic ratio data were obtained from a previous study of 10 subjects [5]. Analysis of CYP2C19 genotypes was performed using PCR amplification followed by restriction endonuclease digestion of genomic DNA from a blood sample.


RESULTS
The intrinsic partial clearance of PG to CG ranged from 0.41-10.11 h-1, and was related to the number of functional CYP2C19 alleles present. Genotypic PMs had metabolic ratios > 13, while genotypic heterozygote EMs had metabolic ratios < 9.


CONCLUSIONS
Proguanil may be a suitable phenotyping probe for the CYP2C19 genetic polymorphism, however the exact antimode of the urinary metabolic ratio chosen to separate poor and extensive metabolisers needs further investigation.
Coller
J K
JK
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Somogyi
A A
AA
Bochner
F
F
D000284:Administration, Oral; D000483:Alleles; D000963:Antimetabolites / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism* / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004262:DNA Restriction Enzymes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D002727:Proguanil / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine*; D044465:White People
D000963:Antimetabolites; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D004262:DNA Restriction Enzymes; D002727:Proguanil