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. Author manuscript; available in PMC: 2017 Jun 1.
Published in final edited form as: Clin Pharmacol Ther. 2016 Jan 12;99(6):642–650. doi: 10.1002/cpt.319

Figure 3.

Figure 3

Urinary recovery of ATX and metabolites. The percentage of the administered dose recovered in 24 h (IM, EM1, EM2) or 72 h (PM) urine collections as ATX (panel A), NDA (panel B) and carboxy metabolites, products of subsequent biotransformation of initial 2-methylhydroxylation (panel C), is presented as a function of the percentage of the administered dose recovered as 4-OH-ATX. Recovery exceeded 100% of the dose in two subjects (~105%). 4-OH-ATX was the most abundant single metabolite recovered in all CYP2D6 genotype groups, but the hydroxycarboxy products of initial 2-methylhydroxylation constituted a considerably larger proportion of overall ATX biotransformation in the PM group. Individual data points are color-coded by genotype (PM, red; IM, yellow; EM1, green; EM2, blue), and the size of the circles represent the apparent oral clearance relative to the largest apparent oral clearance in an individual with three functional CYP2D6 alleles (black symbol); NDA was not detected in the urine of this participant. The extremely small size of the PM data points relative to the reference demonstrates that the increased contribution of 2-hydroxylation in PMs does not “compensate” for the absence of CYP2D6 activity.