Further analysis of sparteine oxidation in a Japanese population and comparison with data observed in different ethnic populations.
1. Data on the oxidation polymorphism of sparteine (SP) studied in 84 unrelated Japanese subjects of whom two (2.4%) were classified as poor metabolizers (PMs) were re-evaluated. The data were obtained from 6-hour urinary excretion ratios of SP to 2- and 5-dehydrosparteines (DHS), after an oral dose of 100 mg of SP sulphate. 2. Urinary excretion of both SP and DHS correlated with the SP/DHS ratio (rs = 0.862 and -0.756, respectively, P less than 0.001). In addition, urinary excretion of 2-DHS, 5-DHS or total DHS discriminated between PMs and extensive metabolizers (EMs). There was also a highly significant correlation (rs = 0.669, P less than 0.001) between the urinary excretion of 2- and 5-DHS. 3. These re-evaluated results on the oxidation polymorphism of SP indicate that 2- and 5-DHS formation from SP shares a common metabolic pathway (presumably via the same P-450 isozyme), and that the SP/DHS ratio, conventionally used as a discriminating index between PMs and EMs, quantitatively reflects the capacity of 2- and 5-DHS formation. 4. The benefit of using a shorter (6 h) collection period for assessing the individual oxidation phenotype of SP and inter-ethnic comparison of SP oxidation is also discussed.
Horai
Y
Y
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Ishizaki
T
T
Eichelbaum
M
M
Hashimoto
K
K
Chiba
K
K
Dengler
H J
HJ
D000328:Adult; D005006:Ethnicity; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D010084:Oxidation-Reduction; D013034:Sparteine / Q000031:analogs & derivatives / Q000652:urine*
C044693:5-dehydrosparteine; D013034:Sparteine; C044694:2-dehydrosparteine