Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil
| Autor: | Osamu Kaneko, Anders Björkman, Yngve Bergqvist, Akira Kaneko, Miho Takechi, Takatoshi Kobayakawa, Takashi Ishizaki, Morris Kalkoa |
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| Rok vydání: | 1999 |
| Předmět: |
Cycloguanil
Adolescent Genotype Proguanil Plasmodium vivax CYP2C19 Pharmacology Mixed Function Oxygenases Antimalarials Cytochrome P-450 Enzyme System parasitic diseases Dihydrofolate reductase medicine Malaria Vivax Immunology and Allergy Humans Malaria Falciparum Child biology Triazines Infant Plasmodium falciparum medicine.disease biology.organism_classification Virology Cytochrome P-450 CYP2C19 Tetrahydrofolate Dehydrogenase Infectious Diseases Child Preschool biology.protein Aryl Hydrocarbon Hydroxylases Malaria medicine.drug |
| Zdroj: | Karolinska Institutet |
| ISSN: | 0022-1899 |
| Popis: | Mutations in human CYP2C19 and parasite dihydrofolate reductase (dhfr) genes, related to poor metabolism of proguanil and resistance to cycloguanil, respectively, have both been assumed to be associated with poor antimalarial effect by proguanil. To study this, 95 subjects with uncomplicated Plasmodium falciparum or Plasmodium vivax infections in Vanuatu received proguanil treatment for 3 days (adult relative dose of 300-500 mg/day) and were followed up for 28 days. A similarly high antimalarial efficacy against both infections was observed in 62 patients with CYP2C19-related poor metabolizer genotype and in 33 with extensive metabolizer genotype, even though blood cycloguanil was significantly more often detected in those with extensive metabolizer genotype than in those with poor metabolizer genotype. All 28 P. falciparum isolates had two dhfr mutations (residues 59 and 108), suggesting moderate resistance to cycloguanil. The results suggest that the parent compound proguanil has significant intrinsic efficacy against falciparum and vivax malaria independent of the metabolite cycloguanil. |
| Databáze: | OpenAIRE |
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