Inter-Subject Variability in the Activation of Proguanil to the Active Cycloguanil in Ghanaians

Abstract

One hundred and thirty-two healthy Ghanaian volunteers were randomly selected and the activation of the anti-malarial drug proguanil (PG) to the active metabolite cycloguanil (CG) was evaluated in them. These volunteers were made up of 16.7% females and 83.3% males. The volunteers were phenotyped either as extensive metabolisers (EMs) or poor metabolisers (PMs) by measuring the proguanil/cycloguanil ratio in their urine following a single dose of the pro-drug. One hundred and twenty-six subjects (97 %) were EMs while 6 subjects (3%) were PMs. The pharmacokinetic parameters of proguanil were not significantly different between 5 EM and 2 PM subjects, although the PM did show a higher plasma proguanil concentration after distribution phase and a longer elimination half-life. Cycloguanil characteristics were not different between the groups as was expected. The prevalence of 3 % of PM phenotype of proguanil metabolism in Ghanaians is comparable to results obtained in Caucasians 36%, but differ from what was obtained in Kenya (35%). This finding suggests a lesser variability of proguanil metabolism in Ghanaians. The maximum average plasma cycloguanil concentration of 93.4ng/ml obtained for the PMs in this study also showed that the metabolite concentrations achieved would be effective against many strains of P. Falciparum.