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Oxidative activation of proguanil and dapsone acetylation in Thai soldiers.
Author(s) -
Edstein MD,
Shanks GD,
TejaIsavadharm P,
Rieckmann KH,
Webster HK
Publication year - 1994
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1994.tb04241.x
Subject(s) - proguanil , dapsone , thais , malaria , pharmacology , medicine , incidence (geometry) , biology , chemistry , chloroquine , immunology , demography , physics , sociology , optics
The prevalence of putative poor metaboliser (PM) phenotypes of proguanil oxidation in Caucasian populations is 3‐10%. The PM frequency in Oriental populations is unknown. In this study the plasma metabolic ratios of proguanil and dapsone to their principal metabolites cycloguanil and monoacetyldapsone were determined in Thai soldiers receiving antifolate drug combinations for malaria prophylaxis. The distribution ratio of proguanil to cycloguanil (PROG/CYC) was highly skewed with no evidence of bimodality. Assuming subjects with a PROG/CYC ratio greater than 10 are PMs from studies in Caucasians, the incidence of PMs in the soldiers would be 18% (30 of 170). The mean PROG/CYC ratio for PMs in the Thai soldiers was 31.2 +/‐ 28.9 (n = 30) compared with 25.5 +/‐ 2.5 (n = 3) in a study of Caucasians. The corresponding values for putative EMs were 5.4 +/‐ 2.1 (n = 140) and 2.4 +/‐ 0.2 (n = 134). Similar to other Oriental populations, Thais were found to be predominantly (76%, 173 of 228) rapid acetylators of dapsone.