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 3­ 6% , 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 £. Falciparum.