Difference in drug concentrations with CYP2C9 metabolizer status and evidence for and against genotyping Only studies involving oral drug administration and adult subjects were included. Case reports were excluded. AUC differences were significant unless otherwise specified.
| Drug | Approximate Difference in Mean/Median Concentrations (AUC) Compared with *1 / *1, Unless Otherwise Stated | Evidence for Genotyping | Evidence against Genotyping | References for Pharmacokinetic Data |
|---|---|---|---|---|
| Celecoxib | Single dose: *1 / *3: 1.4- to 2.2-fold; *3 / *3: 2.2- to 9-fold; *1 / *2, *2 / *2, and *2 / *3: not different; repeated dosing: *3 / *3: 1.0- to 8-fold; *1 / *2, *2 / *2, and *1 / *3: not different | Little evidence for altered effect; relatively high therapeutic index | Tang et al. (2001); Brenner et al. (2003); Kirchheiner et al. (2003e); Stempak et al. (2005); Lundblad et al. (2006) | |
| Fluvastatin | Repeated dosing: 3R,5S-enantiomer (active): *1 / *3: 1.3-fold; *2 / *3: 2.2-fold; *3 / *3: 3.1-fold; *1 / *2 and *2 / *2: not different | Clinical implications unclear; high therapeutic index | Kirchheiner et al. (2003b) | |
| Glimepiride | Single dose: *1 / *3 or *2 / *3: 1.3- to 2.7-fold; *3 / *3: 1.5-fold; *1 / *2: not different | Suggestion of increased hypoglycemia in PM | Implications of active metabolite not known | Niemi et al. (2002); Wang et al. (2005) |
| Glyburide | Single dose: *1 / *3 or *2 / *3: 1.4- to 2.8-fold (N.S. in some studies); *3 / *3: 2.3-fold; *1 / *2 and *2 / *2: not different | Suggestion of increased hypoglycemia in PM | Kirchheiner et al. (2002b); Niemi et al. (2002); Yin et al. (2005) | |
| Ibuprofen | Single dose: *1 / *3: 1.6- to 1.8-fold *2 / *3: 1.4- to 3.0-fold (N.S. in all studies); *3 / *3: 1.8- to 2.7-fold; *1 / *2 and *2 / *2: not different | Clinical implications unclear; relatively high therapeutic index; enantiomers complicate interpretation | Kirchheiner et al. (2002c); Garcia-Martin et al. (2004) | |
| Lornoxicam | Single dose: *1 / *2 or *1 / *3: 1.6- to 1.9-fold; *3 / *13: 39-fold | Clinical implications unclear; relatively high therapeutic index | Zhang et al. (2005b); Liu et al. (2006) | |
| Losartan | Single dose: no significant difference for losartan or E-3174, although latter metabolite was 0.1 fold in *3 / *3 (n = 1) versus *1 / *1; repeated dosing: *1 / *2: 3-fold for losartan | Decreased production of the main active moiety, E-3174, with *3 / *3 genotype suggests lack of effect likely | Fischer et al. (2002); Yasar et al. (2002); Lee et al. (2003b); Sekino et al. (2003) | |
| Phenytoin | Single dose: *1 / *2: 1.5-fold; *2 / *2: 2.7-fold (N.S.); *1 / *3: 1.5-fold; *2 / *3: 2.7-fold (N.S.) | Low therapeutic index; cases of homozygotes for low activity alleles (e.g., *3 / *3) suggest greater effect | Clinical value of genotyping remains to be determined in the context of an extensive history of use with therapeutic drug monitoring | Caraco et al. (2001) |
| Piroxicam | Single dose: *1 / *2: 1.7-fold; *1 / *3: 1.7-fold | Clinical implications unclear; relatively high therapeutic index | Perini et al. (2005) | |
| Tenoxicam | Single dose: *1 / *2: 1.4-fold; *1 / *3: 1.8-fold | Clinical implications unclear; relatively high therapeutic index | Vianna-Jorge et al. (2004) | |
| Tolbutamide | Single dose: *1 / *2: 1.1- to 1.5-fold (N.S. in some studies); *1 / *3: 1.7- to 1.9-fold; *2 / *3: 2.2-fold; *3 / *3: 4.7- to 6.5-fold; *2 / *2: not different | Potentiated hypoglycemic effect in healthy volunteer study | Kirchheiner et al. (2002a); Lee at al. (2002b); Shon et al. (2002); Chen et al. (2005) | |
| Torsemide | Single dose: *1 / *3: 1.5-fold; *2 / *3: 1.7-fold; *3 / *3: 2.8-fold; *1 / *2 and *2 / *2: not different | Data on clinical implications in patients lacking | Vormfelde et al. (2004) |
N.S., not significant