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aBCC2 −24C>T is associated with (a) erythromycin metabolism but not with (b) midazolam metabolism. Erythromycin metabolism was assessed using the erythromycin breath test (ERMBT) 1/T max in 108 subjects, and midazolam metabolism was assessed from intrinsic midazolam clearance (Cl int ) in 30 subjects. The data represent mean values (symbols) and SEM (error bars) for ERMBT, and individual values (symbols), mean values (horizontal lines), and SEM (error bars) for midazolam. *P < 0.05.
Contexts in source publication
Context 1
... specifically focused on variations in the ABCC2 promoter at the −24C>T locus because of its known influence on the functional properties of the encoded protein. 26 In a cohort of 108 subjects for whom DNA samples were available, homozygosity for this variant was associated with a significantly increase in the metabolism of erythromycin (P = 0.013), as determined by the ERMBT parameter 1/ T max (Figure 5a), identified by Rivory et al. 27 as being the most informative value for estimation of hepatic CYP3A4 activity. ...
Context 2
... demographic characteristics at baseline for patients who were homozygous carriers of this SNP were similar to those for patients with the CC-or CT-genotype ( Table 2). Individuals who were heterozygous for the variant were found to have erythromycin metabolism rates that were not significantly different from those in individuals who were homozygous for the reference ABCC2 allele (Figure 5b). None of the other SNPs investigated in ABCC2 was found to be significantly associated with the ERMBT (Supplementary Figure S4 online). ...
Context 3
... after excluding data for the three individuals carrying the SLCO1B3 334TT genotype (all had the ABCC2 −24TT genotype) associated with decreased erythromycin metabolism, 28 the association between ABCC2 −24C>T and ERMBT 1/T max remained significant (P = 0.019) (data not shown). As anticipated from the findings related to cellular transport and to the data for Abcc2(−/−) mice, the ABCC2 −24C>T variant was not associated with the clearance of midazolam in human subjects (Figure 5b). ...
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Breath tests (BTs) have been investigated as diagnostic tools to phenotype drug disposition in cancer patients in the pursuit to individualize drug treatment. The choice of the right phenotype probe is crucial and depends on the metabolic pathway of the anticancer agent of interest. BTs using orally or intravenously administered selective non-radioactive (13)C-labeled probes to non-invasively evaluate dihydropyrimidine dehydrogenase, cytochrome P450 (CYP) 3A4, and CYP2D6 enzyme activity have been published. Clinically, a (13)C-dextromethorphan BT to predict endoxifen levels in breast cancer patients and a (13)C-uracil BT to predict fluoropyrimidine toxicity in colorectal cancer patients are most promising. However, the clinical benefit and cost effectiveness of these phenotype BTs need to be determined in order to make the transition from an experimental setting to clinical practice as companion diagnostic tests.
