Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians
| Autor: | Erik Skjelbo, Theonest K. Mutabingwa, Karin Kramer Nielsen, Kim Brøsen, Lars F. Gram, Ib C. Bygbjerg |
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| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Cycloguanil Proguanil Parasitemia CYP2C19 Urine Biology Pharmacology Tanzania Mixed Function Oxygenases Antimalarials Cytochrome P-450 Enzyme System Chloroquine parasitic diseases medicine Humans Pharmacology (medical) Mephenytoin Aged Malaria prophylaxis Middle Aged medicine.disease Malaria Cytochrome P-450 CYP2C19 Anticonvulsants Female Aryl Hydrocarbon Hydroxylases Oxidation-Reduction medicine.drug |
| Zdroj: | Skjelbo, E, Mutabingwa, T K, Bygbjerg, I, Nielsen, K K, Gram, L F & Brøsen, K 1996, ' Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians ', Clinical Pharmacology and Therapeutics, vol. 59, no. 3, pp. 304-311 . https://doi.org/10.1016/S0009-9236(96)80008-7 |
| DOI: | 10.1016/S0009-9236(96)80008-7 |
| Popis: | S-Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 Tanzanians. The mephenytoin S/R ratio in urine ranged from 0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation between the mephenytoin S/R ratio and the chloroguanide/cycloguanil ratios (r(s) = 0.73; p < 0.00001). This indicates that cytochrome P4502C19 or CYP2C19 is a major enzyme that catalyzes the bioactivation of chloroguanide to cycloguanil. Choroguanide is a pro-drug, and hence a low CYP2C19 activity may lead to prophylactic failure caused by inadequate formation of cycloguanil. Fifty-eight women who previously took either 200 mg chloroguanide daily (n = 26) or 200 mg chloroguanide daily plus 300 mg chloroquine weekly (n = 32) in a malaria chemoprophylaxis study showed that there was a significant correlation between the number of earlier breakthrough parasitemia episodes and the chloroguanide/cycloguanil ratio (r(s) = 0.30; p = 0.02). The breakthrough rate did not correlate with the S/R mephenytoin ratio. However, other factors, such as exposure to mosquitoes and sensitivity of the plasmodium to cycloguanil, are probably more important. |
| Databáze: | OpenAIRE |
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