Dose/Formulationa | Subject Race and Gender | BCRP c.421C>A Number of subjects per Genotype | NAT2 Phenotype | Sulfasalazine AUC Variability | Effect of c.421C>A SNP or BCRP Inhibitor on PK | Reference |
---|---|---|---|---|---|---|
2000-mg IR tablet | Asian men | 12 C/C, 16 C/A, 9 A/A | 13 RA, 16 IA, 8 SA | 1.9-fold (95% CI; genotype controlled) | 1.9-fold AUC increase in 421C/A; 3.5-fold AUC increase in 421A/A; clear gene-dose effect | Yamasaki et al., 2008 |
1000-mg suspension (also tested IR tablet) | Caucasian men and women | 9 C/C, 5 C/A, 0 A/A | Not genotyped; sulfapyridine PK not studied | 20.5-fold (maximum/minimum; genotype controlled) | 2.4-fold AUC increase in 421C/A genotype | Urquhart et al., 2008 |
500-mg enteric-coated tablet | Asian men | 12 C/C, 12 C/A, 12 A/A | 4 RA, 20 IA, 12 SA | 21- to 81-fold (maximum/minimum; genotype controlled) | None (trend for 2-fold AUC increase in A/A genotype; N.S.); no clear gene-dose effect; no significant effect of BCRP inhibitor (40 mg pantoprazole) | Adkison et al., 2010 |
2000-mg/100-μg IR tablet/suspension | Asian men | 8 C/C | Not genotyped; sulfapyridine PK not studied | AUC CV = 24%–40% | Curcumin (2 ga) increased AUC 3.2-fold (therapeutic dose) and 2-fold (microdose) | Kusuhara et al., 2012 |
CI, confidence interval; CV, coefficient of variation; IA, intermediate acetylator; RA, rapid acetylator; SA, slow acetylator.
↵a The route of administration was oral in all cases.