Relationship between proguanil metabolic ratio and CYP2C19 genotype in a Caucasian population.

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Citation

Hoskins JM, Shenfield GM, Gross AS

Relationship between proguanil metabolic ratio and CYP2C19 genotype in a Caucasian population.

Br J Clin Pharmacol. 1998 Nov;46(5):499-504. doi: 10.1046/j.1365-2125.1998.00807.x.

PubMed ID
9833604 [ View in PubMed
]
Abstract

AIMS: To investigate the relationship between proguanil metabolic ratio (MR, proguanil/cycloguanil) and CYP2C19 genotype in a Caucasian population. METHODS: Ninety-nine Caucasians (age range: 18-55 years, 54 female, 45 male) were genotyped for CYP2C19 and phenotyped for proguanil oxidation by collecting urine for 8 h after taking 100 mg proguanil hydrochloride. Proguanil and cycloguanil concentrations were measured by h.p.l.c. PCR was employed for CYP2C19 genotyping. RESULTS: The three (3%) individuals who were homozygous for CYP2C19*2 (*2/*2) had the highest proguanil MRs (range: 8.0-134.6). Seventy-three (74%) individuals were homozygous for the wild-type allele (*1/*1) and 23 (23%) were heterozygous (*1/*2). The *1/*1 individuals had lower MRs (median=1.4, range: 0.23-5.9, P=0.003, Mann-Whitney U-test) than the *1/*2 subjects (median=2.5, range: 0.88-7.3). CONCLUSIONS: A CYP2C19 gene-dose effect for proguanil oxidation to cycloguanil was observed, confirming a role for CYP2C19 in cycloguanil formation in vivo. However, there was substantial overlap of proguanil MRs in subjects of different CYP2C19 genotypes, due possibly to variability in the activity of other enzymes contributing to the formation of cycloguanil.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
ProguanilCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details