Evidence for a dissociation in the control of sparteine, debrisoquine and metoprolol metabolism in Nigerians.
The 0-8 hour urinary distributions of the metabolic ratios of sparteine (100 mg), debrisoquine (10 mg) and metoprolol (100 mg) were measured in 165 healthy, unrelated, black Nigerian medical students. There was a weak correlation (rs = 0.51, p < 0.001; n = 82) between the metoprolol/alpha-hydroxymetoprolol (M/HM) and the sparteine/total (2- + 5-) dehydrosparteine (S/DHS) ratios. No significant correlations were found between the debrisoquine/4-hydroxydebrisoquine (D/HD) and M/HM ratios (rs = 0.16, n = 33) and between the D/HD and S/DHS ratios (rs = 0.31, n = 38). Both visual inspection and kernel density analysis of the data suggested the presence of two phenotypic groups for sparteine oxidation, with 4% of the population studied being putative poor metabolizers. In contrast biomodality was not apparent in the distribution of the log10M/HM and log10D/HD ratios. These findings provide evidence for a dissociation in the control of metoprolol, sparteine and debrisoquine oxidation in Nigerians and highlight the difficulties in the interpretation of data from pharmacogenetic studies in different ethnic groups.
Lennard
M S
MS
University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK.
Iyun
A O
AO
Jackson
P R
PR
Tucker
G T
GT
Woods
H F
HF
D000328:Adult; D044383:Black People / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009549:Nigeria; D010641:Phenotype; D011110:Polymorphism, Genetic; D013034:Sparteine / Q000378:metabolism*
D013034:Sparteine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol; D003647:Debrisoquin