Effects of genetic variation at the CYP2C19/CYP2C9 locus on pharmacokinetics of chlorcycloguanil in adult Gambians.
Pharmacogenomics
; 10(9): 1423-31, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19761366
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 317 vs 216 ng.h/ml; ratio of geometric means 1.46; 95% CI 1.03 to 2.09; p = 0.0363) and higher C(max) (geometric mean ratio 1.52; 95% CI 1.13 to 2.05; p = 0.0071).CONCLUSION:
CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triazinas
/
Hidrocarburo de Aril Hidroxilasas
/
Proguanil
/
Antimaláricos
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Africa
Idioma:
En
Revista:
Pharmacogenomics
Asunto de la revista:
FARMACOLOGIA
/
GENETICA MEDICA
Año:
2009
Tipo del documento:
Article