Effects of genetic variation at the CYP2C19/CYP2C9 locus on pharmacokinetics of chlorcycloguanil in adult Gambians.

ABSTRACT:

Aims

Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation at the CYP2C locus might affect pharmacokinetics and so treatment outcome for malaria.

Materials & methods

Polymorphisms in CYP2C19 and CYP2C9 in 43 adult Gambians treated with chlorproguanil/dapsone for uncomplicated malaria were assessed. Chlorcycloguanil pharmacokinetics were measured and associations with CYP2C19 and CYP2C9 alleles and CYP2C19 metabolizer groups investigated.

Results

All CYP2C19/CYP2C9 alleles obeyed Hardy-Weinberg equilibrium. There were 15 CYP2C19/2C9 haplotypes with a common haplotype frequency of 0.23. Participants with the CYP2C19*17 allele had higher chlorcycloguanil area under the concentration versus curve at 24 h (AUC(0-24)) than those without (geometric means

SUBMITTER: Janha RE 

PROVIDER: S-EPMC3870622 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature