Mt. Kinirons et al., ABSENCE OF CORRELATIONS AMONG 3 PUTATIVE IN-VIVO PROBES OF HUMAN CYTOCHROME-P4503A ACTIVITY IN YOUNG HEALTHY-MEN, Clinical pharmacology and therapeutics, 54(6), 1993, pp. 621-629
In vitro studies with human liver microsomes have shown that erythromy
cin N-demethylation, dapsone N-hydroxylation, and the 60-hydroxylation
of cortisol are all primarily mediated by P4503A4. Trait measurements
to assess the in vivo level of activity of these separate oxidations
have also been developed previously. This study investigated the relat
ionships among the three phenotypic trait measurements in 30 young hea
lthy white men. The frequency distributions of the trait values were a
ll unimodal, with a twofold range for the erythromycin breath test and
the urinary dapsone recovery ratio; the urinary 6beta-hydroxycortisol
/cortisol ratio was more variable, with a 17-fold range of values. No
statistically significant correlations were observed among any of the
trait measurements (dapsone recovery ratio versus erythromycin breath
test: r = -0.07, p = 0.7; urinary 6beta-hydroxycortisol/cortisol ratio
versus erythromycin breath test: r = -0.12, p = 0.6; urinary 6beta-hy
droxycortisol/cortisol ratio versus dapsone recovery ratio: r = 0.13,
p = 0.5. This lack of any relationship was unexpected and the reason(s
) is unknown; however, it is possible that factors such as route of ad
ministration and extrahepatic metabolism in the intestinal epithelium
and kidney are involved. Further studies are required to identify and
validate the use of an appropriate in vivo probe of P4503A4 in humans.