Polymorphic oxidative metabolism of proguanil in a Nigerian population.
OBJECTIVE
The genetic polymorphic metabolic oxidation of proguanil was investigated in 126 healthy, unrelated Nigerian subjects as an indication of the phenotypic status of CYP2C19 in Nigerians.


METHODS
The proguanil oxidation capacity was determined using the 8-h urinary metabolic ratio of the parent drug and its metabolite (cycloguanil) after a single oral dose of 200 mg proguanil.


RESULTS
The frequency distribution of the proguanil metabolic ratio ranged from 0.01 to 39.64 with a median of 1.38 in the 126 Nigerians. On the basis of the antimode value of 10 for the proguanil/cycloguanil ratio, the prevalence of poor metabolisers in this Nigerian population was estimated to be 4.8% (6 of 126), which is very similar to that of S-mephenytoin (4.3%) found in a previous study in Nigerians. The data also demonstrated enormous inter-individual differences in the urinary proguanil/cycloguanil ratios with poor metabolisers excreting, on average, only about 8% of the quantity of cycloguanil excreted by extensive metabolisers.


CONCLUSIONS
The incidence of phenotypically poor metabolisers of proguanil in this Nigerian population is similar to those reported for Caucasian and other African populations but is much lower than those reported for Orientals. The study further supports previous studies that proguanil can be used as an alternative probe to phenotype for CYP2C19 activity.
Bolaji
O O
OO
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria. obolaji@oauife.edu.ng
Sadare
I O
IO
Babalola
C P
CP
Ogunbona
F A
FA
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D009549:Nigeria; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D002727:Proguanil / Q000378:metabolism*
D000962:Antimalarials; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D002727:Proguanil